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  • 1
    Publication Date: 2010-12-03
    Description: Haematopoietic stem cells (HSCs) can convert between growth states that have marked differences in bioenergetic needs. Although often quiescent in adults, these cells become proliferative upon physiological demand. Balancing HSC energetics in response to nutrient availability and growth state is poorly understood, yet essential for the dynamism of the haematopoietic system. Here we show that the Lkb1 tumour suppressor is critical for the maintenance of energy homeostasis in haematopoietic cells. Lkb1 inactivation in adult mice causes loss of HSC quiescence followed by rapid depletion of all haematopoietic subpopulations. Lkb1-deficient bone marrow cells exhibit mitochondrial defects, alterations in lipid and nucleotide metabolism, and depletion of cellular ATP. The haematopoietic effects are largely independent of Lkb1 regulation of AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling. Instead, these data define a central role for Lkb1 in restricting HSC entry into cell cycle and in broadly maintaining energy homeostasis in haematopoietic cells through a novel metabolic checkpoint.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037591/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037591/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gurumurthy, Sushma -- Xie, Stephanie Z -- Alagesan, Brinda -- Kim, Judith -- Yusuf, Rushdia Z -- Saez, Borja -- Tzatsos, Alexandros -- Ozsolak, Fatih -- Milos, Patrice -- Ferrari, Francesco -- Park, Peter J -- Shirihai, Orian S -- Scadden, David T -- Bardeesy, Nabeel -- DK050234/DK/NIDDK NIH HHS/ -- R01 DK050234/DK/NIDDK NIH HHS/ -- R01 DK050234-12/DK/NIDDK NIH HHS/ -- R01 DK050234-13/DK/NIDDK NIH HHS/ -- R01 HG005230/HG/NHGRI NIH HHS/ -- R01 HG005230-01/HG/NHGRI NIH HHS/ -- U01 CA141576-01/CA/NCI NIH HHS/ -- England -- Nature. 2010 Dec 2;468(7324):659-63. doi: 10.1038/nature09572.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Center and Center for Regenerative Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21124451" target="_blank"〉PubMed〈/a〉
    Keywords: AMP-Activated Protein Kinases/metabolism ; Adenosine Triphosphate/metabolism ; Animals ; Apoptosis ; Autophagy ; Bone Marrow/metabolism/pathology ; Cell Cycle ; Cell Proliferation ; Cell Survival ; *Energy Metabolism ; Enzyme Activation ; Female ; Hematopoiesis ; Hematopoietic Stem Cells/*cytology/*metabolism/pathology ; Homeostasis ; Lipid Metabolism ; Male ; Membrane Potential, Mitochondrial ; Mice ; Mice, Inbred C57BL ; Mitochondria/metabolism/pathology ; Multiprotein Complexes ; Protein-Serine-Threonine Kinases/deficiency/genetics/*metabolism ; Proteins/antagonists & inhibitors/metabolism ; TOR Serine-Threonine Kinases/metabolism ; Tumor Suppressor Proteins/deficiency/genetics/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2011-09-09
    Description: The calcium-transporting ATPase ATP2A2, also known as SERCA2a, is a critical ATPase responsible for Ca(2+) re-uptake during excitation-contraction coupling. Impaired Ca(2+) uptake resulting from decreased expression and reduced activity of SERCA2a is a hallmark of heart failure. Accordingly, restoration of SERCA2a expression by gene transfer has proved to be effective in improving cardiac function in heart-failure patients, as well as in animal models. The small ubiquitin-related modifier (SUMO) can be conjugated to lysine residues of target proteins, and is involved in many cellular processes. Here we show that SERCA2a is SUMOylated at lysines 480 and 585 and that this SUMOylation is essential for preserving SERCA2a ATPase activity and stability in mouse and human cells. The levels of SUMO1 and the SUMOylation of SERCA2a itself were greatly reduced in failing hearts. SUMO1 restitution by adeno-associated-virus-mediated gene delivery maintained the protein abundance of SERCA2a and markedly improved cardiac function in mice with heart failure. This effect was comparable to SERCA2A gene delivery. Moreover, SUMO1 overexpression in isolated cardiomyocytes augmented contractility and accelerated Ca(2+) decay. Transgene-mediated SUMO1 overexpression rescued cardiac dysfunction induced by pressure overload concomitantly with increased SERCA2a function. By contrast, downregulation of SUMO1 using small hairpin RNA (shRNA) accelerated pressure-overload-induced deterioration of cardiac function and was accompanied by decreased SERCA2a function. However, knockdown of SERCA2a resulted in severe contractile dysfunction both in vitro and in vivo, which was not rescued by overexpression of SUMO1. Taken together, our data show that SUMOylation is a critical post-translational modification that regulates SERCA2a function, and provide a platform for the design of novel therapeutic strategies for heart failure.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3443490/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3443490/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kho, Changwon -- Lee, Ahyoung -- Jeong, Dongtak -- Oh, Jae Gyun -- Chaanine, Antoine H -- Kizana, Eddy -- Park, Woo Jin -- Hajjar, Roger J -- HL080498/HL/NHLBI NIH HHS/ -- HL093183/HL/NHLBI NIH HHS/ -- P20 HL100396/HL/NHLBI NIH HHS/ -- P20 HL100396-02/HL/NHLBI NIH HHS/ -- P20HL100396/HL/NHLBI NIH HHS/ -- R01 HL078731/HL/NHLBI NIH HHS/ -- R01 HL078731-04/HL/NHLBI NIH HHS/ -- R01 HL080498/HL/NHLBI NIH HHS/ -- R01 HL080498-05/HL/NHLBI NIH HHS/ -- R01 HL083156/HL/NHLBI NIH HHS/ -- R01 HL083156-05/HL/NHLBI NIH HHS/ -- R01 HL088434/HL/NHLBI NIH HHS/ -- R01 HL088434-02/HL/NHLBI NIH HHS/ -- England -- Nature. 2011 Sep 7;477(7366):601-5. doi: 10.1038/nature10407.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cardiovascular Research Center, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, Box 1030, New York, New York 10029, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21900893" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; HEK293 Cells ; Heart Failure/*metabolism/physiopathology ; Humans ; Lysine/metabolism ; Mice ; Rats ; Rats, Sprague-Dawley ; SUMO-1 Protein/genetics/*metabolism ; Sarcoplasmic Reticulum Calcium-Transporting ATPases/*metabolism ; *Sumoylation ; Sus scrofa
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2013-05-31
    Description: Many neurodegenerative disorders, such as Alzheimer's, Parkinson's and polyglutamine diseases, share a common pathogenic mechanism: the abnormal accumulation of disease-causing proteins, due to either the mutant protein's resistance to degradation or overexpression of the wild-type protein. We have developed a strategy to identify therapeutic entry points for such neurodegenerative disorders by screening for genetic networks that influence the levels of disease-driving proteins. We applied this approach, which integrates parallel cell-based and Drosophila genetic screens, to spinocerebellar ataxia type 1 (SCA1), a disease caused by expansion of a polyglutamine tract in ataxin 1 (ATXN1). Our approach revealed that downregulation of several components of the RAS-MAPK-MSK1 pathway decreases ATXN1 levels and suppresses neurodegeneration in Drosophila and mice. Importantly, pharmacological inhibitors of components of this pathway also decrease ATXN1 levels, suggesting that these components represent new therapeutic targets in mitigating SCA1. Collectively, these data reveal new therapeutic entry points for SCA1 and provide a proof-of-principle for tackling other classes of intractable neurodegenerative diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4020154/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4020154/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Park, Jeehye -- Al-Ramahi, Ismael -- Tan, Qiumin -- Mollema, Nissa -- Diaz-Garcia, Javier R -- Gallego-Flores, Tatiana -- Lu, Hsiang-Chih -- Lagalwar, Sarita -- Duvick, Lisa -- Kang, Hyojin -- Lee, Yoontae -- Jafar-Nejad, Paymaan -- Sayegh, Layal S -- Richman, Ronald -- Liu, Xiuyun -- Gao, Yan -- Shaw, Chad A -- Arthur, J Simon C -- Orr, Harry T -- Westbrook, Thomas F -- Botas, Juan -- Zoghbi, Huda Y -- HD024064/HD/NICHD NIH HHS/ -- MC_U127081014/Medical Research Council/United Kingdom -- NS42179/NS/NINDS NIH HHS/ -- P30 HD024064/HD/NICHD NIH HHS/ -- R01 NS027699/NS/NINDS NIH HHS/ -- R01 NS042179/NS/NINDS NIH HHS/ -- T32 GM007526/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Jun 20;498(7454):325-31. doi: 10.1038/nature12204. Epub 2013 May 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23719381" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; Ataxin-1 ; Ataxins ; Cell Line, Tumor ; Disease Models, Animal ; Down-Regulation/drug effects ; Drosophila melanogaster/genetics/*metabolism ; Female ; Humans ; MAP Kinase Signaling System/drug effects ; Male ; Mice ; Mitogen-Activated Protein Kinases/*metabolism ; Molecular Sequence Data ; Molecular Targeted Therapy ; Nerve Tissue Proteins/chemistry/genetics/*metabolism/*toxicity ; Nuclear Proteins/chemistry/genetics/*metabolism/*toxicity ; Phosphorylation ; Protein Stability/drug effects ; Ribosomal Protein S6 Kinases, 90-kDa/deficiency/genetics/*metabolism ; Spinocerebellar Ataxias/*metabolism/*pathology ; Transgenes ; ras Proteins/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2010-12-24
    Description: Chromatin is composed of DNA and a variety of modified histones and non-histone proteins, which have an impact on cell differentiation, gene regulation and other key cellular processes. Here we present a genome-wide chromatin landscape for Drosophila melanogaster based on eighteen histone modifications, summarized by nine prevalent combinatorial patterns. Integrative analysis with other data (non-histone chromatin proteins, DNase I hypersensitivity, GRO-Seq reads produced by engaged polymerase, short/long RNA products) reveals discrete characteristics of chromosomes, genes, regulatory elements and other functional domains. We find that active genes display distinct chromatin signatures that are correlated with disparate gene lengths, exon patterns, regulatory functions and genomic contexts. We also demonstrate a diversity of signatures among Polycomb targets that include a subset with paused polymerase. This systematic profiling and integrative analysis of chromatin signatures provides insights into how genomic elements are regulated, and will serve as a resource for future experimental investigations of genome structure and function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109908/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109908/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kharchenko, Peter V -- Alekseyenko, Artyom A -- Schwartz, Yuri B -- Minoda, Aki -- Riddle, Nicole C -- Ernst, Jason -- Sabo, Peter J -- Larschan, Erica -- Gorchakov, Andrey A -- Gu, Tingting -- Linder-Basso, Daniela -- Plachetka, Annette -- Shanower, Gregory -- Tolstorukov, Michael Y -- Luquette, Lovelace J -- Xi, Ruibin -- Jung, Youngsook L -- Park, Richard W -- Bishop, Eric P -- Canfield, Theresa K -- Sandstrom, Richard -- Thurman, Robert E -- MacAlpine, David M -- Stamatoyannopoulos, John A -- Kellis, Manolis -- Elgin, Sarah C R -- Kuroda, Mitzi I -- Pirrotta, Vincenzo -- Karpen, Gary H -- Park, Peter J -- R01 GM071923/GM/NIGMS NIH HHS/ -- R01 GM082798/GM/NIGMS NIH HHS/ -- R01 HG004037/HG/NHGRI NIH HHS/ -- R37 GM45744/GM/NIGMS NIH HHS/ -- RC1 HG005334/HG/NHGRI NIH HHS/ -- RC2 HG005639/HG/NHGRI NIH HHS/ -- U01 HG004258/HG/NHGRI NIH HHS/ -- U01 HG004258-04/HG/NHGRI NIH HHS/ -- U01 HG004279/HG/NHGRI NIH HHS/ -- U01HG004258/HG/NHGRI NIH HHS/ -- U54 HG004592/HG/NHGRI NIH HHS/ -- England -- Nature. 2011 Mar 24;471(7339):480-5. doi: 10.1038/nature09725. Epub 2010 Dec 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21179089" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Chromatin/*genetics/*metabolism ; Chromatin Immunoprecipitation ; Chromosomal Proteins, Non-Histone/analysis/metabolism ; Deoxyribonuclease I/metabolism ; Drosophila Proteins/genetics ; Drosophila melanogaster/embryology/*genetics/growth & development ; Exons/genetics ; Gene Expression Regulation/genetics ; Genes, Insect/genetics ; Genome, Insect/genetics ; Histones/chemistry/metabolism ; Male ; Molecular Sequence Annotation ; Oligonucleotide Array Sequence Analysis ; Polycomb Repressive Complex 1 ; RNA/analysis/genetics ; Sequence Analysis ; Transcription, Genetic/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2011-10-14
    Description: The naked mole rat (Heterocephalus glaber) is a strictly subterranean, extraordinarily long-lived eusocial mammal. Although it is the size of a mouse, its maximum lifespan exceeds 30 years, making this animal the longest-living rodent. Naked mole rats show negligible senescence, no age-related increase in mortality, and high fecundity until death. In addition to delayed ageing, they are resistant to both spontaneous cancer and experimentally induced tumorigenesis. Naked mole rats pose a challenge to the theories that link ageing, cancer and redox homeostasis. Although characterized by significant oxidative stress, the naked mole rat proteome does not show age-related susceptibility to oxidative damage or increased ubiquitination. Naked mole rats naturally reside in large colonies with a single breeding female, the 'queen', who suppresses the sexual maturity of her subordinates. They also live in full darkness, at low oxygen and high carbon dioxide concentrations, and are unable to sustain thermogenesis nor feel certain types of pain. Here we report the sequencing and analysis of the naked mole rat genome, which reveals unique genome features and molecular adaptations consistent with cancer resistance, poikilothermy, hairlessness and insensitivity to low oxygen, and altered visual function, circadian rythms and taste sensing. This information provides insights into the naked mole rat's exceptional longevity and ability to live in hostile conditions, in the dark and at low oxygen. The extreme traits of the naked mole rat, together with the reported genome and transcriptome information, offer opportunities for understanding ageing and advancing other areas of biological and biomedical research.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319411/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319411/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Eun Bae -- Fang, Xiaodong -- Fushan, Alexey A -- Huang, Zhiyong -- Lobanov, Alexei V -- Han, Lijuan -- Marino, Stefano M -- Sun, Xiaoqing -- Turanov, Anton A -- Yang, Pengcheng -- Yim, Sun Hee -- Zhao, Xiang -- Kasaikina, Marina V -- Stoletzki, Nina -- Peng, Chunfang -- Polak, Paz -- Xiong, Zhiqiang -- Kiezun, Adam -- Zhu, Yabing -- Chen, Yuanxin -- Kryukov, Gregory V -- Zhang, Qiang -- Peshkin, Leonid -- Yang, Lan -- Bronson, Roderick T -- Buffenstein, Rochelle -- Wang, Bo -- Han, Changlei -- Li, Qiye -- Chen, Li -- Zhao, Wei -- Sunyaev, Shamil R -- Park, Thomas J -- Zhang, Guojie -- Wang, Jun -- Gladyshev, Vadim N -- AG021518/AG/NIA NIH HHS/ -- AG038004/AG/NIA NIH HHS/ -- CA080946/CA/NCI NIH HHS/ -- R01 AG021518/AG/NIA NIH HHS/ -- R01 AG021518-10/AG/NIA NIH HHS/ -- R01 AG038004/AG/NIA NIH HHS/ -- R01 AG038004-02/AG/NIA NIH HHS/ -- R01 CA080946/CA/NCI NIH HHS/ -- R01 CA080946-11/CA/NCI NIH HHS/ -- England -- Nature. 2011 Oct 12;479(7372):223-7. doi: 10.1038/nature10533.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioinspired Science, Ewha Womans University, Seoul, 120-750, Korea.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21993625" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological/*genetics ; Aging/genetics ; Amino Acid Sequence ; Animals ; Body Temperature Regulation/genetics ; Carbon Dioxide/analysis/metabolism ; Circadian Rhythm/genetics ; Darkness ; Genes/genetics ; Genome/*genetics ; Genomic Instability/genetics ; Genomics ; Humans ; Ion Channels/genetics ; Longevity/*genetics/physiology ; Male ; Mitochondrial Proteins/genetics ; Mole Rats/*genetics/*physiology ; Molecular Sequence Data ; Mutagenesis/genetics ; Oxygen/analysis/metabolism ; Taste/genetics ; Transcriptome/genetics ; Visual Perception/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2011-03-04
    Description: The evolution of sex chromosomes has resulted in numerous species in which females inherit two X chromosomes but males have a single X, thus requiring dosage compensation. MSL (Male-specific lethal) complex increases transcription on the single X chromosome of Drosophila males to equalize expression of X-linked genes between the sexes. The biochemical mechanisms used for dosage compensation must function over a wide dynamic range of transcription levels and differential expression patterns. It has been proposed that the MSL complex regulates transcriptional elongation to control dosage compensation, a model subsequently supported by mapping of the MSL complex and MSL-dependent histone 4 lysine 16 acetylation to the bodies of X-linked genes in males, with a bias towards 3' ends. However, experimental analysis of MSL function at the mechanistic level has been challenging owing to the small magnitude of the chromosome-wide effect and the lack of an in vitro system for biochemical analysis. Here we use global run-on sequencing (GRO-seq) to examine the specific effect of the MSL complex on RNA Polymerase II (RNAP II) on a genome-wide level. Results indicate that the MSL complex enhances transcription by facilitating the progression of RNAP II across the bodies of active X-linked genes. Improving transcriptional output downstream of typical gene-specific controls may explain how dosage compensation can be imposed on the diverse set of genes along an entire chromosome.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3076316/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3076316/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Larschan, Erica -- Bishop, Eric P -- Kharchenko, Peter V -- Core, Leighton J -- Lis, John T -- Park, Peter J -- Kuroda, Mitzi I -- GM082798/GM/NIGMS NIH HHS/ -- GM45744/GM/NIGMS NIH HHS/ -- HG4845/HG/NHGRI NIH HHS/ -- R01 HG004845/HG/NHGRI NIH HHS/ -- R01 HG004845-01/HG/NHGRI NIH HHS/ -- R01 HG004845-02/HG/NHGRI NIH HHS/ -- R37 GM045744/GM/NIGMS NIH HHS/ -- England -- Nature. 2011 Mar 3;471(7336):115-8. doi: 10.1038/nature09757.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21368835" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Animals ; Cell Line ; Chromosomes, Insect/*genetics/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Dosage Compensation, Genetic/*genetics ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster/enzymology/*genetics ; Genes, Insect/genetics ; Genes, X-Linked/genetics ; Histones/chemistry/metabolism ; Male ; Nuclear Proteins/genetics/metabolism ; RNA Polymerase II/metabolism ; Sequence Analysis, DNA ; Transcription Factors/genetics/metabolism ; *Transcription, Genetic/genetics ; X Chromosome/*genetics/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2014-03-29
    Description: Heart failure is characterized by a debilitating decline in cardiac function, and recent clinical trial results indicate that improving the contractility of heart muscle cells by boosting intracellular calcium handling might be an effective therapy. MicroRNAs (miRNAs) are dysregulated in heart failure but whether they control contractility or constitute therapeutic targets remains speculative. Using high-throughput functional screening of the human microRNAome, here we identify miRNAs that suppress intracellular calcium handling in heart muscle by interacting with messenger RNA encoding the sarcoplasmic reticulum calcium uptake pump SERCA2a (also known as ATP2A2). Of 875 miRNAs tested, miR-25 potently delayed calcium uptake kinetics in cardiomyocytes in vitro and was upregulated in heart failure, both in mice and humans. Whereas adeno-associated virus 9 (AAV9)-mediated overexpression of miR-25 in vivo resulted in a significant loss of contractile function, injection of an antisense oligonucleotide (antagomiR) against miR-25 markedly halted established heart failure in a mouse model, improving cardiac function and survival relative to a control antagomiR oligonucleotide. These data reveal that increased expression of endogenous miR-25 contributes to declining cardiac function during heart failure and suggest that it might be targeted therapeutically to restore function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4131725/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4131725/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wahlquist, Christine -- Jeong, Dongtak -- Rojas-Munoz, Agustin -- Kho, Changwon -- Lee, Ahyoung -- Mitsuyama, Shinichi -- van Mil, Alain -- Park, Woo Jin -- Sluijter, Joost P G -- Doevendans, Pieter A F -- Hajjar, Roger J -- Mercola, Mark -- HHSN268201000045C/HL/NHLBI NIH HHS/ -- HHSN26820100045C/PHS HHS/ -- P01 HL098053/HL/NHLBI NIH HHS/ -- P01HL098053/HL/NHLBI NIH HHS/ -- P20 HL100396/HL/NHLBI NIH HHS/ -- P20HL100396/HL/NHLBI NIH HHS/ -- P30 AR061303/AR/NIAMS NIH HHS/ -- P30 CA030199/CA/NCI NIH HHS/ -- P30AR061303/AR/NIAMS NIH HHS/ -- P30CA030199/CA/NCI NIH HHS/ -- P50 HL112324/HL/NHLBI NIH HHS/ -- P50HL112324/HL/NHLBI NIH HHS/ -- R01 HL088434/HL/NHLBI NIH HHS/ -- R01 HL093183/HL/NHLBI NIH HHS/ -- R01 HL108176/HL/NHLBI NIH HHS/ -- R01 HL113601/HL/NHLBI NIH HHS/ -- R01HL088434/HL/NHLBI NIH HHS/ -- R01HL093183/HL/NHLBI NIH HHS/ -- R01HL108176/HL/NHLBI NIH HHS/ -- R01HL113601/HL/NHLBI NIH HHS/ -- S10 RR021084/RR/NCRR NIH HHS/ -- England -- Nature. 2014 Apr 24;508(7497):531-5. doi: 10.1038/nature13073. Epub 2014 Mar 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Bioengineering, University of California, San Diego, and the Muscle Development and Regeneration Program, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA [2]. ; 1] The Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA [2]. ; Department of Bioengineering, University of California, San Diego, and the Muscle Development and Regeneration Program, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA. ; The Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA. ; 1] Department of Bioengineering, University of California, San Diego, and the Muscle Development and Regeneration Program, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA [2] Department of Cardiology, University Medical Center Utrecht and ICIN Netherlands Heart Institute, Heidelberglaan 100, room G02.523, 3584 CX Utrecht, The Netherlands. ; Global Research Laboratory, Gwangju Institute of Science and Technology, 123 Cheomdan-gwagiro, Buk-gu, Gwangju 500-712, South Korea. ; Department of Cardiology, University Medical Center Utrecht and ICIN Netherlands Heart Institute, Heidelberglaan 100, room G02.523, 3584 CX Utrecht, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670661" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/metabolism ; Dependovirus/genetics ; Disease Models, Animal ; HEK293 Cells ; Heart/drug effects/physiology/physiopathology ; Heart Failure/*genetics/*therapy ; Humans ; Kinetics ; Male ; Mice ; MicroRNAs/analysis/*antagonists & inhibitors/genetics/metabolism ; Myocardial Contraction/*drug effects ; Myocardium/metabolism ; Myocytes, Cardiac/metabolism ; Oligonucleotides, Antisense/genetics/metabolism/pharmacology ; RNA, Messenger/genetics/metabolism ; Sarcoplasmic Reticulum/metabolism ; Sarcoplasmic Reticulum Calcium-Transporting ATPases/genetics/metabolism ; Survival Analysis ; Up-Regulation/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2014-08-29
    Description: Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms. Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths. To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227084/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227084/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ho, Joshua W K -- Jung, Youngsook L -- Liu, Tao -- Alver, Burak H -- Lee, Soohyun -- Ikegami, Kohta -- Sohn, Kyung-Ah -- Minoda, Aki -- Tolstorukov, Michael Y -- Appert, Alex -- Parker, Stephen C J -- Gu, Tingting -- Kundaje, Anshul -- Riddle, Nicole C -- Bishop, Eric -- Egelhofer, Thea A -- Hu, Sheng'en Shawn -- Alekseyenko, Artyom A -- Rechtsteiner, Andreas -- Asker, Dalal -- Belsky, Jason A -- Bowman, Sarah K -- Chen, Q Brent -- Chen, Ron A-J -- Day, Daniel S -- Dong, Yan -- Dose, Andrea C -- Duan, Xikun -- Epstein, Charles B -- Ercan, Sevinc -- Feingold, Elise A -- Ferrari, Francesco -- Garrigues, Jacob M -- Gehlenborg, Nils -- Good, Peter J -- Haseley, Psalm -- He, Daniel -- Herrmann, Moritz -- Hoffman, Michael M -- Jeffers, Tess E -- Kharchenko, Peter V -- Kolasinska-Zwierz, Paulina -- Kotwaliwale, Chitra V -- Kumar, Nischay -- Langley, Sasha A -- Larschan, Erica N -- Latorre, Isabel -- Libbrecht, Maxwell W -- Lin, Xueqiu -- Park, Richard -- Pazin, Michael J -- Pham, Hoang N -- Plachetka, Annette -- Qin, Bo -- Schwartz, Yuri B -- Shoresh, Noam -- Stempor, Przemyslaw -- Vielle, Anne -- Wang, Chengyang -- Whittle, Christina M -- Xue, Huiling -- Kingston, Robert E -- Kim, Ju Han -- Bernstein, Bradley E -- Dernburg, Abby F -- Pirrotta, Vincenzo -- Kuroda, Mitzi I -- Noble, William S -- Tullius, Thomas D -- Kellis, Manolis -- MacAlpine, David M -- Strome, Susan -- Elgin, Sarah C R -- Liu, Xiaole Shirley -- Lieb, Jason D -- Ahringer, Julie -- Karpen, Gary H -- Park, Peter J -- 092096/Wellcome Trust/United Kingdom -- 101863/Wellcome Trust/United Kingdom -- 54523/Wellcome Trust/United Kingdom -- 5RL9EB008539/EB/NIBIB NIH HHS/ -- K99 HG006259/HG/NHGRI NIH HHS/ -- K99HG006259/HG/NHGRI NIH HHS/ -- R01 GM098461/GM/NIGMS NIH HHS/ -- R01 HG004037/HG/NHGRI NIH HHS/ -- R37 GM048405/GM/NIGMS NIH HHS/ -- T32 GM071340/GM/NIGMS NIH HHS/ -- T32 HG002295/HG/NHGRI NIH HHS/ -- U01 HG004258/HG/NHGRI NIH HHS/ -- U01 HG004270/HG/NHGRI NIH HHS/ -- U01 HG004279/HG/NHGRI NIH HHS/ -- U01 HG004695/HG/NHGRI NIH HHS/ -- U01HG004258/HG/NHGRI NIH HHS/ -- U01HG004270/HG/NHGRI NIH HHS/ -- U01HG004279/HG/NHGRI NIH HHS/ -- U01HG004695/HG/NHGRI NIH HHS/ -- U54 CA121852/CA/NCI NIH HHS/ -- U54 HG004570/HG/NHGRI NIH HHS/ -- U54 HG006991/HG/NHGRI NIH HHS/ -- U54CA121852/CA/NCI NIH HHS/ -- U54HG004570/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Aug 28;512(7515):449-52. doi: 10.1038/nature13415.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA [3] [4] Victor Chang Cardiac Research Institute and The University of New South Wales, Sydney, New South Wales 2052, Australia (J.W.K.H.); Department of Biochemistry, University at Buffalo, Buffalo, New York 14203, USA (T.L.); Department of Molecular Biology and Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08540, USA (K.I., T.E.J.); Department of Human Genetics, University of Chicago, Chicago, Illinois 06037, USA (J.D.L.); Division of Genomic Technologies, Center for Life Science Technologies, RIKEN, Yokohama 230-0045, Japan (A.M.); Department of Genetics, Department of Computer Science, Stanford University, Stanford, California 94305, USA (A.K.); Department of Biology, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA (N.C.R.). ; 1] Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA [3]. ; 1] Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, 450 Brookline Avenue, Boston, Massachusetts 02215, USA [3] [4] Victor Chang Cardiac Research Institute and The University of New South Wales, Sydney, New South Wales 2052, Australia (J.W.K.H.); Department of Biochemistry, University at Buffalo, Buffalo, New York 14203, USA (T.L.); Department of Molecular Biology and Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08540, USA (K.I., T.E.J.); Department of Human Genetics, University of Chicago, Chicago, Illinois 06037, USA (J.D.L.); Division of Genomic Technologies, Center for Life Science Technologies, RIKEN, Yokohama 230-0045, Japan (A.M.); Department of Genetics, Department of Computer Science, Stanford University, Stanford, California 94305, USA (A.K.); Department of Biology, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA (N.C.R.). ; Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Department of Biology and Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA [2] Victor Chang Cardiac Research Institute and The University of New South Wales, Sydney, New South Wales 2052, Australia (J.W.K.H.); Department of Biochemistry, University at Buffalo, Buffalo, New York 14203, USA (T.L.); Department of Molecular Biology and Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08540, USA (K.I., T.E.J.); Department of Human Genetics, University of Chicago, Chicago, Illinois 06037, USA (J.D.L.); Division of Genomic Technologies, Center for Life Science Technologies, RIKEN, Yokohama 230-0045, Japan (A.M.); Department of Genetics, Department of Computer Science, Stanford University, Stanford, California 94305, USA (A.K.); Department of Biology, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA (N.C.R.). ; 1] Department of Information and Computer Engineering, Ajou University, Suwon 443-749, Korea [2] Systems Biomedical Informatics Research Center, College of Medicine, Seoul National University, Seoul 110-799, Korea. ; 1] Department of Genome Dynamics, Life Sciences Division, Lawrence Berkeley National Lab, Berkeley, California 94720, USA [2] Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA [3] Victor Chang Cardiac Research Institute and The University of New South Wales, Sydney, New South Wales 2052, Australia (J.W.K.H.); Department of Biochemistry, University at Buffalo, Buffalo, New York 14203, USA (T.L.); Department of Molecular Biology and Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08540, USA (K.I., T.E.J.); Department of Human Genetics, University of Chicago, Chicago, Illinois 06037, USA (J.D.L.); Division of Genomic Technologies, Center for Life Science Technologies, RIKEN, Yokohama 230-0045, Japan (A.M.); Department of Genetics, Department of Computer Science, Stanford University, Stanford, California 94305, USA (A.K.); Department of Biology, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA (N.C.R.). ; 1] Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA [3] Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. ; The Gurdon Institute and Department of Genetics, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK. ; 1] National Institute of General Medical Sciences, National Institutes of Health, Bethesda, Maryland 20892, USA [2] National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Department of Biology, Washington University in St. Louis, St. Louis, Missouri 63130, USA. ; 1] Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2] Broad Institute, Cambridge, Massachusetts 02141, USA [3] Victor Chang Cardiac Research Institute and The University of New South Wales, Sydney, New South Wales 2052, Australia (J.W.K.H.); Department of Biochemistry, University at Buffalo, Buffalo, New York 14203, USA (T.L.); Department of Molecular Biology and Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08540, USA (K.I., T.E.J.); Department of Human Genetics, University of Chicago, Chicago, Illinois 06037, USA (J.D.L.); Division of Genomic Technologies, Center for Life Science Technologies, RIKEN, Yokohama 230-0045, Japan (A.M.); Department of Genetics, Department of Computer Science, Stanford University, Stanford, California 94305, USA (A.K.); Department of Biology, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA (N.C.R.). ; 1] Department of Biology, Washington University in St. Louis, St. Louis, Missouri 63130, USA [2] Victor Chang Cardiac Research Institute and The University of New South Wales, Sydney, New South Wales 2052, Australia (J.W.K.H.); Department of Biochemistry, University at Buffalo, Buffalo, New York 14203, USA (T.L.); Department of Molecular Biology and Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08540, USA (K.I., T.E.J.); Department of Human Genetics, University of Chicago, Chicago, Illinois 06037, USA (J.D.L.); Division of Genomic Technologies, Center for Life Science Technologies, RIKEN, Yokohama 230-0045, Japan (A.M.); Department of Genetics, Department of Computer Science, Stanford University, Stanford, California 94305, USA (A.K.); Department of Biology, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA (N.C.R.). ; 1] Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Program in Bioinformatics, Boston University, Boston, Massachusetts 02215, USA. ; Department of Molecular, Cell and Developmental Biology, University of California Santa Cruz, Santa Cruz, California 95064, USA. ; Department of Bioinformatics, School of Life Science and Technology, Tongji University, Shanghai 200092, China. ; 1] Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854, USA [2] Food Science and Technology Department, Faculty of Agriculture, Alexandria University, 21545 El-Shatby, Alexandria, Egypt. ; Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA. ; Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. ; Department of Biology and Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. ; 1] Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Harvard/MIT Division of Health Sciences and Technology, Cambridge, Massachusetts 02139, USA. ; Department of Anatomy Physiology and Cell Biology, University of California Davis, Davis, California 95616, USA. ; Broad Institute, Cambridge, Massachusetts 02141, USA. ; 1] Department of Biology and Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA [2] Department of Biology, Center for Genomics and Systems Biology, New York University, New York, New York 10003, USA. ; National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. ; 1] Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Broad Institute, Cambridge, Massachusetts 02141, USA. ; 1] Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA. ; Princess Margaret Cancer Centre, Toronto, Ontario M6G 1L7, Canada. ; 1] Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA [2] Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA. ; 1] Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2] Broad Institute, Cambridge, Massachusetts 02141, USA. ; 1] Department of Genome Dynamics, Life Sciences Division, Lawrence Berkeley National Lab, Berkeley, California 94720, USA [2] Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA. ; Department of Molecular Biology, Cellular Biology and Biochemistry, Brown University, Providence, Rhode Island 02912, USA. ; Department of Computer Science and Engineering, University of Washington, Seattle, Washington 98195, USA. ; 1] Department of Genome Dynamics, Life Sciences Division, Lawrence Berkeley National Lab, Berkeley, California 94720, USA [2] Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA [3] Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA. ; 1] Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854, USA [2] Department of Molecular Biology, Umea University, 901 87 Umea, Sweden. ; 1] Systems Biomedical Informatics Research Center, College of Medicine, Seoul National University, Seoul 110-799, Korea [2] Seoul National University Biomedical Informatics, Division of Biomedical Informatics, College of Medicine, Seoul National University, Seoul 110-799, Korea. ; 1] Broad Institute, Cambridge, Massachusetts 02141, USA [2] Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA [3] Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. ; Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854, USA. ; 1] Department of Computer Science and Engineering, University of Washington, Seattle, Washington 98195, USA [2] Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA. ; 1] Program in Bioinformatics, Boston University, Boston, Massachusetts 02215, USA [2] Department of Chemistry, Boston University, Boston, Massachusetts 02215, USA. ; 1] Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, 450 Brookline Avenue, Boston, Massachusetts 02215, USA [3] Broad Institute, Cambridge, Massachusetts 02141, USA. ; 1] Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA [3] Informatics Program, Children's Hospital, Boston, Massachusetts 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25164756" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis elegans/*cytology/*genetics ; Cell Line ; Centromere/genetics/metabolism ; Chromatin/chemistry/*genetics/*metabolism ; Chromatin Assembly and Disassembly/genetics ; DNA Replication/genetics ; Drosophila melanogaster/*cytology/*genetics ; Enhancer Elements, Genetic/genetics ; Epigenesis, Genetic ; Heterochromatin/chemistry/genetics/metabolism ; Histones/chemistry/metabolism ; Humans ; Molecular Sequence Annotation ; Nuclear Lamina/metabolism ; Nucleosomes/chemistry/genetics/metabolism ; Promoter Regions, Genetic/genetics ; Species Specificity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2010-12-24
    Description: To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192495/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192495/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉modENCODE Consortium -- Roy, Sushmita -- Ernst, Jason -- Kharchenko, Peter V -- Kheradpour, Pouya -- Negre, Nicolas -- Eaton, Matthew L -- Landolin, Jane M -- Bristow, Christopher A -- Ma, Lijia -- Lin, Michael F -- Washietl, Stefan -- Arshinoff, Bradley I -- Ay, Ferhat -- Meyer, Patrick E -- Robine, Nicolas -- Washington, Nicole L -- Di Stefano, Luisa -- Berezikov, Eugene -- Brown, Christopher D -- Candeias, Rogerio -- Carlson, Joseph W -- Carr, Adrian -- Jungreis, Irwin -- Marbach, Daniel -- Sealfon, Rachel -- Tolstorukov, Michael Y -- Will, Sebastian -- Alekseyenko, Artyom A -- Artieri, Carlo -- Booth, Benjamin W -- Brooks, Angela N -- Dai, Qi -- Davis, Carrie A -- Duff, Michael O -- Feng, Xin -- Gorchakov, Andrey A -- Gu, Tingting -- Henikoff, Jorja G -- Kapranov, Philipp -- Li, Renhua -- MacAlpine, Heather K -- Malone, John -- Minoda, Aki -- Nordman, Jared -- Okamura, Katsutomo -- Perry, Marc -- Powell, Sara K -- Riddle, Nicole C -- Sakai, Akiko -- Samsonova, Anastasia -- Sandler, Jeremy E -- Schwartz, Yuri B -- Sher, Noa -- Spokony, Rebecca -- Sturgill, David -- van Baren, Marijke -- Wan, Kenneth H -- Yang, Li -- Yu, Charles -- Feingold, Elise -- Good, Peter -- Guyer, Mark -- Lowdon, Rebecca -- Ahmad, Kami -- Andrews, Justen -- Berger, Bonnie -- Brenner, Steven E -- Brent, Michael R -- Cherbas, Lucy -- Elgin, Sarah C R -- Gingeras, Thomas R -- Grossman, Robert -- Hoskins, Roger A -- Kaufman, Thomas C -- Kent, William -- Kuroda, Mitzi I -- Orr-Weaver, Terry -- Perrimon, Norbert -- Pirrotta, Vincenzo -- Posakony, James W -- Ren, Bing -- Russell, Steven -- Cherbas, Peter -- Graveley, Brenton R -- Lewis, Suzanna -- Micklem, Gos -- Oliver, Brian -- Park, Peter J -- Celniker, Susan E -- Henikoff, Steven -- Karpen, Gary H -- Lai, Eric C -- MacAlpine, David M -- Stein, Lincoln D -- White, Kevin P -- Kellis, Manolis -- R01 HG004037/HG/NHGRI NIH HHS/ -- R01HG004037/HG/NHGRI NIH HHS/ -- RC2HG005639/HG/NHGRI NIH HHS/ -- U01 HG004258/HG/NHGRI NIH HHS/ -- U01 HG004271/HG/NHGRI NIH HHS/ -- U01 HG004279/HG/NHGRI NIH HHS/ -- U01HG004258/HG/NHGRI NIH HHS/ -- U01HG004261/HG/NHGRI NIH HHS/ -- U01HG004264/HG/NHGRI NIH HHS/ -- U01HG004271/HG/NHGRI NIH HHS/ -- U01HG004274/HG/NHGRI NIH HHS/ -- U01HG004279/HG/NHGRI NIH HHS/ -- U41HG004269/HG/NHGRI NIH HHS/ -- ZIA DK015600-14/Intramural NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Dec 24;330(6012):1787-97. doi: 10.1126/science.1198374. Epub 2010 Dec 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21177974" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; *Chromatin/genetics/metabolism ; Computational Biology/methods ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster/*genetics/growth & development/metabolism ; Epigenesis, Genetic ; Gene Expression Regulation ; *Gene Regulatory Networks ; Genes, Insect ; *Genome, Insect ; Genomics/methods ; Histones/metabolism ; *Molecular Sequence Annotation ; Nucleosomes/genetics/metabolism ; Promoter Regions, Genetic ; RNA, Small Untranslated/genetics/metabolism ; Transcription Factors/metabolism ; Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2010-10-23
    Description: Mosquitoes in the Anopheles gambiae complex show rapid ecological and behavioral diversification, traits that promote malaria transmission and complicate vector control efforts. A high-density, genome-wide mosquito SNP-genotyping array allowed mapping of genomic differentiation between populations and species that exhibit varying levels of reproductive isolation. Regions near centromeres or within polymorphic inversions exhibited the greatest genetic divergence, but divergence was also observed elsewhere in the genomes. Signals of natural selection within populations were overrepresented among genomic regions that are differentiated between populations, implying that differentiation is often driven by population-specific selective events. Complex genomic differentiation among speciating vector mosquito populations implies that tools for genome-wide monitoring of population structure will prove useful for the advancement of malaria eradication.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Neafsey, D E -- Lawniczak, M K N -- Park, D J -- Redmond, S N -- Coulibaly, M B -- Traore, S F -- Sagnon, N -- Costantini, C -- Johnson, C -- Wiegand, R C -- Collins, F H -- Lander, E S -- Wirth, D F -- Kafatos, F C -- Besansky, N J -- Christophides, G K -- Muskavitch, M A T -- 077229/Z/05/Z/Wellcome Trust/United Kingdom -- BB/E002641/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2010 Oct 22;330(6003):514-7. doi: 10.1126/science.1193036.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Broad Institute, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20966254" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anopheles gambiae/*genetics ; Female ; *Gene Flow ; *Genes, Insect ; Genotype ; Insect Vectors/*genetics ; Malaria ; Polymorphism, Single Nucleotide/*genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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