ALBERT

Description: Alzheimer's disease (AD) is a severe age-related neurodegenerative disorder characterized by accumulation of amyloid-beta plaques and neurofibrillary tangles, synaptic and neuronal loss, and cognitive decline. Several genes have been implicated in AD, but chromatin state alterations during neurodegeneration remain uncharacterized. Here we profile transcriptional and chromatin state dynamics across early and late pathology in the hippocampus of an inducible mouse model of AD-like neurodegeneration. We find a coordinated downregulation of synaptic plasticity genes and regulatory regions, and upregulation of immune response genes and regulatory regions, which are targeted by factors that belong to the ETS family of transcriptional regulators, including PU.1. Human regions orthologous to increasing-level enhancers show immune-cell-specific enhancer signatures as well as immune cell expression quantitative trait loci, while decreasing-level enhancer orthologues show fetal-brain-specific enhancer activity. Notably, AD-associated genetic variants are specifically enriched in increasing-level enhancer orthologues, implicating immune processes in AD predisposition. Indeed, increasing enhancers overlap known AD loci lacking protein-altering variants, and implicate additional loci that do not reach genome-wide significance. Our results reveal new insights into the mechanisms of neurodegeneration and establish the mouse as a useful model for functional studies of AD regulatory regions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530583/" 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/PMC4530583/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gjoneska, Elizabeta -- Pfenning, Andreas R -- Mathys, Hansruedi -- Quon, Gerald -- Kundaje, Anshul -- Tsai, Li-Huei -- Kellis, Manolis -- R01 HG004037/HG/NHGRI NIH HHS/ -- R01 NS078839/NS/NINDS NIH HHS/ -- R01HG004037-07/HG/NHGRI NIH HHS/ -- R01NS078839/NS/NINDS NIH HHS/ -- RC1 HG005334/HG/NHGRI NIH HHS/ -- RC1HG005334/HG/NHGRI NIH HHS/ -- England -- Nature. 2015 Feb 19;518(7539):365-9. doi: 10.1038/nature14252.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2] Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA. ; 1] Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA [2] Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. ; The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. ; 1] Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA [2] Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [3] Department of Genetics, Department of Computer Science, Stanford University, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25693568" target="_blank"〉PubMed〈/a〉

Description: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530010/" 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/PMC4530010/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roadmap Epigenomics Consortium -- Kundaje, Anshul -- Meuleman, Wouter -- Ernst, Jason -- Bilenky, Misha -- Yen, Angela -- Heravi-Moussavi, Alireza -- Kheradpour, Pouya -- Zhang, Zhizhuo -- Wang, Jianrong -- Ziller, Michael J -- Amin, Viren -- Whitaker, John W -- Schultz, Matthew D -- Ward, Lucas D -- Sarkar, Abhishek -- Quon, Gerald -- Sandstrom, Richard S -- Eaton, Matthew L -- Wu, Yi-Chieh -- Pfenning, Andreas R -- Wang, Xinchen -- Claussnitzer, Melina -- Liu, Yaping -- Coarfa, Cristian -- Harris, R Alan -- Shoresh, Noam -- Epstein, Charles B -- Gjoneska, Elizabeta -- Leung, Danny -- Xie, Wei -- Hawkins, R David -- Lister, Ryan -- Hong, Chibo -- Gascard, Philippe -- Mungall, Andrew J -- Moore, Richard -- Chuah, Eric -- Tam, Angela -- Canfield, Theresa K -- Hansen, R Scott -- Kaul, Rajinder -- Sabo, Peter J -- Bansal, Mukul S -- Carles, Annaick -- Dixon, Jesse R -- Farh, Kai-How -- Feizi, Soheil -- Karlic, Rosa -- Kim, Ah-Ram -- Kulkarni, Ashwinikumar -- Li, Daofeng -- Lowdon, Rebecca -- Elliott, GiNell -- Mercer, Tim R -- Neph, Shane J -- Onuchic, Vitor -- Polak, Paz -- Rajagopal, Nisha -- Ray, Pradipta -- Sallari, Richard C -- Siebenthall, Kyle T -- Sinnott-Armstrong, Nicholas A -- Stevens, Michael -- Thurman, Robert E -- Wu, Jie -- Zhang, Bo -- Zhou, Xin -- Beaudet, Arthur E -- Boyer, Laurie A -- De Jager, Philip L -- Farnham, Peggy J -- Fisher, Susan J -- Haussler, David -- Jones, Steven J M -- Li, Wei -- Marra, Marco A -- McManus, Michael T -- Sunyaev, Shamil -- Thomson, James A -- Tlsty, Thea D -- Tsai, Li-Huei -- Wang, Wei -- Waterland, Robert A -- Zhang, Michael Q -- Chadwick, Lisa H -- Bernstein, Bradley E -- Costello, Joseph F -- Ecker, Joseph R -- Hirst, Martin -- Meissner, Alexander -- Milosavljevic, Aleksandar -- Ren, Bing -- Stamatoyannopoulos, John A -- Wang, Ting -- Kellis, Manolis -- 5R24HD000836/HD/NICHD NIH HHS/ -- ES017166/ES/NIEHS NIH HHS/ -- F32 HL110473/HL/NHLBI NIH HHS/ -- F32HL110473/HL/NHLBI NIH HHS/ -- K99 HL119617/HL/NHLBI NIH HHS/ -- K99HL119617/HL/NHLBI NIH HHS/ -- P01 DA008227/DA/NIDA NIH HHS/ -- P30AG10161/AG/NIA NIH HHS/ -- P50 MH096890/MH/NIMH NIH HHS/ -- R01 AG015819/AG/NIA NIH HHS/ -- R01 AG017917/AG/NIA NIH HHS/ -- R01 ES024984/ES/NIEHS NIH HHS/ -- R01 ES024992/ES/NIEHS NIH HHS/ -- R01 HG004037/HG/NHGRI NIH HHS/ -- R01 HG007175/HG/NHGRI NIH HHS/ -- R01 HG007354/HG/NHGRI NIH HHS/ -- R01AG15819/AG/NIA NIH HHS/ -- R01AG17917/AG/NIA NIH HHS/ -- R01HG004037/HG/NHGRI NIH HHS/ -- R01HG004037-S1/HG/NHGRI NIH HHS/ -- R01NS078839/NS/NINDS NIH HHS/ -- RC1HG005334/HG/NHGRI NIH HHS/ -- RF1 AG015819/AG/NIA NIH HHS/ -- T32 ES007032/ES/NIEHS NIH HHS/ -- T32 GM007198/GM/NIGMS NIH HHS/ -- T32 GM007266/GM/NIGMS NIH HHS/ -- T32 GM081739/GM/NIGMS NIH HHS/ -- U01 ES017154/ES/NIEHS NIH HHS/ -- U01AG46152/AG/NIA NIH HHS/ -- U01DA025956/DA/NIDA NIH HHS/ -- U01ES017154/ES/NIEHS NIH HHS/ -- U01ES017155/ES/NIEHS NIH HHS/ -- U01ES017156/ES/NIEHS NIH HHS/ -- U01ES017166/ES/NIEHS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Feb 19;518(7539):317-30. doi: 10.1038/nature14248.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA. [2] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [3] Department of Genetics, Department of Computer Science, 300 Pasteur Dr., Lane Building, L301, Stanford, California 94305-5120, USA. ; 1] Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA. [2] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. ; 1] Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA. [2] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [3] Department of Biological Chemistry, University of California, Los Angeles, 615 Charles E Young Dr South, Los Angeles, California 90095, USA. ; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada. ; 1] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [2] Department of Stem Cell and Regenerative Biology, 7 Divinity Ave, Cambridge, Massachusetts 02138, USA. ; Epigenome Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA. ; Department of Cellular and Molecular Medicine, Institute of Genomic Medicine, Moores Cancer Center, Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA. ; Genomic Analysis Laboratory, Howard Hughes Medical Institute &The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, California 92037, USA. ; Department of Genome Sciences, University of Washington, 3720 15th Ave. NE, Seattle, Washington 98195, USA. ; 1] Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA. [2] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [3] Biology Department, Massachusetts Institute of Technology, 31 Ames St, Cambridge, Massachusetts 02142, USA. ; The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. ; 1] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [2] The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 43 Vassar St, Cambridge, Massachusetts 02139, USA. ; 1] Department of Cellular and Molecular Medicine, Institute of Genomic Medicine, Moores Cancer Center, Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA. [2] Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093, USA. ; Department of Neurosurgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 1450 3rd Street, San Francisco, California 94158, USA. ; Department of Pathology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, California 94143-0511, USA. ; Department of Medicine, Division of Medical Genetics, University of Washington, 2211 Elliot Avenue, Seattle, Washington 98121, USA. ; 1] Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA. [2] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [3] Department of Computer Science &Engineering, University of Connecticut, 371 Fairfield Way, Storrs, Connecticut 06269, USA. ; Department of Microbiology and Immunology and Centre for High-Throughput Biology, University of British Columbia, 2125 East Mall, Vancouver, British Columbia V6T 1Z4, Canada. ; Bioinformatics Group, Department of Molecular Biology, Division of Biology, Faculty of Science, University of Zagreb, Horvatovac 102a, 10000 Zagreb, Croatia. ; Department of Molecular and Cell Biology, Center for Systems Biology, The University of Texas, Dallas, NSERL, RL10, 800 W Campbell Road, Richardson, Texas 75080, USA. ; Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University in St Louis, 4444 Forest Park Ave, St Louis, Missouri 63108, USA. ; Institute for Molecular Bioscience, University of Queensland, St Lucia, Queensland 4072, Australia. ; 1] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [2] Brigham &Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA. ; 1] Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University in St Louis, 4444 Forest Park Ave, St Louis, Missouri 63108, USA. [2] Department of Computer Science and Engineeering, Washington University in St. Louis, St. Louis, Missouri 63130, USA. ; 1] Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York 11794-3600, USA. [2] Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. ; Molecular and Human Genetics Department, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA. ; Biology Department, Massachusetts Institute of Technology, 31 Ames St, Cambridge, Massachusetts 02142, USA. ; 1] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [2] Brigham &Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA. [3] Harvard Medical School, 25 Shattuck St, Boston, Massachusetts 02115, USA. ; Department of Biochemistry, Keck School of Medicine, University of Southern California, 1450 Biggy Street, Los Angeles, California 90089-9601, USA. ; ObGyn, Reproductive Sciences, University of California San Francisco, 35 Medical Center Way, San Francisco, California 94143, USA. ; Center for Biomolecular Sciences and Engineering, University of Santa Cruz, 1156 High Street, Santa Cruz, California 95064, USA. ; 1] Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada. [2] Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia V5A 1S6, Canada. [3] Department of Medical Genetics, University of British Columbia, 2329 West Mall, Vancouver, BC, Canada, V6T 1Z4. ; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA. ; 1] Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada. [2] Department of Medical Genetics, University of British Columbia, 2329 West Mall, Vancouver, BC, Canada, V6T 1Z4. ; Department of Microbiology and Immunology, Diabetes Center, University of California, San Francisco, 513 Parnassus Ave, San Francisco, California 94143-0534, USA. ; 1] University of Wisconsin, Madison, Wisconsin 53715, USA. [2] Morgridge Institute for Research, 330 N. Orchard Street, Madison, Wisconsin 53707, USA. ; USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, 1100 Bates Street, Houston, Texas 77030, USA. ; 1] Department of Molecular and Cell Biology, Center for Systems Biology, The University of Texas, Dallas, NSERL, RL10, 800 W Campbell Road, Richardson, Texas 75080, USA. [2] Bioinformatics Division, Center for Synthetic and Systems Biology, TNLIST, Tsinghua University, Beijing 100084, China. ; National Institute of Environmental Health Sciences, 111 T.W. Alexander Drive, Research Triangle Park, North Carolina 27709, USA. ; 1] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [2] Massachusetts General Hospital, 55 Fruit St, Boston, Massachusetts 02114, USA. [3] Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, Maryland 20815-6789, USA. ; 1] Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada. [2] Department of Microbiology and Immunology and Centre for High-Throughput Biology, University of British Columbia, 2125 East Mall, Vancouver, British Columbia V6T 1Z4, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25693563" target="_blank"〉PubMed〈/a〉

Description: Songbirds represent an important model organism for elucidating molecular mechanisms that link genes with complex behaviors, in part because they have discrete vocal learning circuits that have parallels with those that mediate human speech. We found that ~10% of the genes in the avian genome were regulated by singing, and we found a striking regional diversity of both basal and singing-induced programs in the four key song nuclei of the zebra finch, a vocal learning songbird. The region-enriched patterns were a result of distinct combinations of region-enriched transcription factors (TFs), their binding motifs, and presinging acetylation of histone 3 at lysine 27 (H3K27ac) enhancer activity in the regulatory regions of the associated genes. RNA interference manipulations validated the role of the calcium-response transcription factor (CaRF) in regulating genes preferentially expressed in specific song nuclei in response to singing. Thus, differential combinatorial binding of a small group of activity-regulated TFs and predefined epigenetic enhancer activity influences the anatomical diversity of behaviorally regulated gene networks.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359888/" 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/PMC4359888/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Whitney, Osceola -- Pfenning, Andreas R -- Howard, Jason T -- Blatti, Charles A -- Liu, Fang -- Ward, James M -- Wang, Rui -- Audet, Jean-Nicoles -- Kellis, Manolis -- Mukherjee, Sayan -- Sinha, Saurabh -- Hartemink, Alexander J -- West, Anne E -- Jarvis, Erich D -- 5T32MH018882-18/MH/NIMH NIH HHS/ -- R01 DC007218/DC/NIDCD NIH HHS/ -- R01 HG004037/HG/NHGRI NIH HHS/ -- R01DC007218/DC/NIDCD NIH HHS/ -- R21 NS084336/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Dec 12;346(6215):1256780. doi: 10.1126/science.1256780.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Howard Hughes Medical Institute, and Duke University Medical Center, Durham, NC 27710, USA. owhitney@gmail.com apfenning@csail.mit.edu west@neuro.duke.edu jarvis@neuro.duke.edu. ; Department of Neurobiology, Howard Hughes Medical Institute, and Duke University Medical Center, Durham, NC 27710, USA. Computer Science and Artificial Intelligence Laboratory and the Broad Institute of MIT and Harvard, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. owhitney@gmail.com apfenning@csail.mit.edu west@neuro.duke.edu jarvis@neuro.duke.edu. ; Department of Neurobiology, Howard Hughes Medical Institute, and Duke University Medical Center, Durham, NC 27710, USA. ; Department of Computer Science, University of Illinois, Urbana-Champaign, IL, USA. ; Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA. ; Department of Biology, McGill University, Montreal, Quebec H3A 1B1, Canada. ; Computer Science and Artificial Intelligence Laboratory and the Broad Institute of MIT and Harvard, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Department of Statistics, Duke University, Durham, NC, USA. ; Department of Computer Science, Duke University, Durham, NC 27708-0129, USA. ; Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA. owhitney@gmail.com apfenning@csail.mit.edu west@neuro.duke.edu jarvis@neuro.duke.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25504732" target="_blank"〉PubMed〈/a〉

Description: Song-learning birds and humans share independently evolved similarities in brain pathways for vocal learning that are essential for song and speech and are not found in most other species. Comparisons of brain transcriptomes of song-learning birds and humans relative to vocal nonlearners identified convergent gene expression specializations in specific song and speech brain regions of avian vocal learners and humans. The strongest shared profiles relate bird motor and striatal song-learning nuclei, respectively, with human laryngeal motor cortex and parts of the striatum that control speech production and learning. Most of the associated genes function in motor control and brain connectivity. Thus, convergent behavior and neural connectivity for a complex trait are associated with convergent specialized expression of multiple genes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4385736/" 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/PMC4385736/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pfenning, Andreas R -- Hara, Erina -- Whitney, Osceola -- Rivas, Miriam V -- Wang, Rui -- Roulhac, Petra L -- Howard, Jason T -- Wirthlin, Morgan -- Lovell, Peter V -- Ganapathy, Ganeshkumar -- Mouncastle, Jacquelyn -- Moseley, M Arthur -- Thompson, J Will -- Soderblom, Erik J -- Iriki, Atsushi -- Kato, Masaki -- Gilbert, M Thomas P -- Zhang, Guojie -- Bakken, Trygve -- Bongaarts, Angie -- Bernard, Amy -- Lein, Ed -- Mello, Claudio V -- Hartemink, Alexander J -- Jarvis, Erich D -- DP1 OD000448/OD/NIH HHS/ -- R01 DC007218/DC/NIDCD NIH HHS/ -- R01DC007218/DC/NIDCD NIH HHS/ -- R21 DC007478/DC/NIDCD NIH HHS/ -- R24 GM092842/GM/NIGMS NIH HHS/ -- R24GM092842/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Dec 12;346(6215):1256846. doi: 10.1126/science.1256846.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Howard Hughes Medical Institute, and Duke University Medical Center, Durham, NC 27710, USA. apfenning@csail.mit.edu amink@cs.duke.edu jarvis@neuro.duke.edu. ; Department of Neurobiology, Howard Hughes Medical Institute, and Duke University Medical Center, Durham, NC 27710, USA. ; Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA. ; Duke Proteomics and Metabolomics Core Facility, Center for Genomic and Computational Biology, Duke University Medical Center, Durham, NC 27710, USA. ; Laboratory for Symbolic Cognitive Development, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, 1350 Copenhagen, Denmark. Trace and Environmental DNA Laboratory, Department of Environment and Agriculture, Curtin University, Perth, Western Australia 6102, Australia. ; China National GeneBank, BGI-Shenzhen, Shenzhen 518083, China. Centre for Social Evolution, Department of Biology, University of Copenhagen, DK-2100 Copenhagen, Denmark. ; Allen Institute for Brain Science, Seattle, WA 98103, USA. ; Department of Computer Science, Duke University, Durham, NC 27708, USA. apfenning@csail.mit.edu amink@cs.duke.edu jarvis@neuro.duke.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25504733" target="_blank"〉PubMed〈/a〉

Description: The zebra finch is an important model organism in several fields with unique relevance to human neuroscience. Like other songbirds, the zebra finch communicates through learned vocalizations, an ability otherwise documented only in humans and a few other animals and lacking in the chicken-the only bird with a sequenced genome until now. Here we present a structural, functional and comparative analysis of the genome sequence of the zebra finch (Taeniopygia guttata), which is a songbird belonging to the large avian order Passeriformes. We find that the overall structures of the genomes are similar in zebra finch and chicken, but they differ in many intrachromosomal rearrangements, lineage-specific gene family expansions, the number of long-terminal-repeat-based retrotransposons, and mechanisms of sex chromosome dosage compensation. We show that song behaviour engages gene regulatory networks in the zebra finch brain, altering the expression of long non-coding RNAs, microRNAs, transcription factors and their targets. We also show evidence for rapid molecular evolution in the songbird lineage of genes that are regulated during song experience. These results indicate an active involvement of the genome in neural processes underlying vocal communication and identify potential genetic substrates for the evolution and regulation of this behaviour.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3187626/" 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/PMC3187626/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Warren, Wesley C -- Clayton, David F -- Ellegren, Hans -- Arnold, Arthur P -- Hillier, Ladeana W -- Kunstner, Axel -- Searle, Steve -- White, Simon -- Vilella, Albert J -- Fairley, Susan -- Heger, Andreas -- Kong, Lesheng -- Ponting, Chris P -- Jarvis, Erich D -- Mello, Claudio V -- Minx, Pat -- Lovell, Peter -- Velho, Tarciso A F -- Ferris, Margaret -- Balakrishnan, Christopher N -- Sinha, Saurabh -- Blatti, Charles -- London, Sarah E -- Li, Yun -- Lin, Ya-Chi -- George, Julia -- Sweedler, Jonathan -- Southey, Bruce -- Gunaratne, Preethi -- Watson, Michael -- Nam, Kiwoong -- Backstrom, Niclas -- Smeds, Linnea -- Nabholz, Benoit -- Itoh, Yuichiro -- Whitney, Osceola -- Pfenning, Andreas R -- Howard, Jason -- Volker, Martin -- Skinner, Bejamin M -- Griffin, Darren K -- Ye, Liang -- McLaren, William M -- Flicek, Paul -- Quesada, Victor -- Velasco, Gloria -- Lopez-Otin, Carlos -- Puente, Xose S -- Olender, Tsviya -- Lancet, Doron -- Smit, Arian F A -- Hubley, Robert -- Konkel, Miriam K -- Walker, Jerilyn A -- Batzer, Mark A -- Gu, Wanjun -- Pollock, David D -- Chen, Lin -- Cheng, Ze -- Eichler, Evan E -- Stapley, Jessica -- Slate, Jon -- Ekblom, Robert -- Birkhead, Tim -- Burke, Terry -- Burt, David -- Scharff, Constance -- Adam, Iris -- Richard, Hugues -- Sultan, Marc -- Soldatov, Alexey -- Lehrach, Hans -- Edwards, Scott V -- Yang, Shiaw-Pyng -- Li, Xiaoching -- Graves, Tina -- Fulton, Lucinda -- Nelson, Joanne -- Chinwalla, Asif -- Hou, Shunfeng -- Mardis, Elaine R -- Wilson, Richard K -- BB/D013704/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/E010652/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/F007590/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BBE0175091/Biotechnology and Biological Sciences Research Council/United Kingdom -- BBS/E/I/00001425/Biotechnology and Biological Sciences Research Council/United Kingdom -- MC_U137761446/Medical Research Council/United Kingdom -- P30 DA018310/DA/NIDA NIH HHS/ -- R01 DC007218/DC/NIDCD NIH HHS/ -- R01 GM059290/GM/NIGMS NIH HHS/ -- R01 GM085233/GM/NIGMS NIH HHS/ -- R01 GM59290/GM/NIGMS NIH HHS/ -- R01 HG002939/HG/NHGRI NIH HHS/ -- R01 NS045264/NS/NINDS NIH HHS/ -- R01NS051820/NS/NINDS NIH HHS/ -- U54 HG003079/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Apr 1;464(7289):757-62. doi: 10.1038/nature08819.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Genome Center, Washington University School of Medicine, Campus Box 8501, 4444 Forest Park Avenue, St Louis, Missouri 63108, USA. wwarren@watson.wustl.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20360741" target="_blank"〉PubMed〈/a〉

Description: Sodium appetite is an instinct that involves avid specific intention. It is elicited by sodium deficiency, stress-evoked adrenocorticotropic hormone (ACTH), and reproduction. Genome-wide microarrays in sodium-deficient mice or after ACTH infusion showed up-regulation of hypothalamic genes, including dopamine- and cAMP-regulated neuronal phosphoprotein 32 kDa (DARPP-32), dopamine receptors-1 and -2, α-2C- adrenoceptor, and striatally enriched protein tyrosine phosphatase (STEP). Both DARPP-32 and neural plasticity regulator activity-regulated cytoskeleton associated protein (ARC) were up-regulated in lateral hypothalamic orexinergic neurons by sodium deficiency. Administration of dopamine D1 (SCH23390) and D2 receptor (raclopride) antagonists reduced gratification of sodium appetite triggered by sodium deficiency. SCH23390 was specific, having no effect on osmotic-induced water drinking, whereas raclopride also reduced water intake. D1 receptor KO mice had normal sodium appetite, indicating compensatory regulation. Appetite was insensitive to SCH23390, confirming the absence of off-target effects. Bilateral microinjection of SCH23390 (100 nM in 200 nL) into rats’ lateral hypothalamus greatly reduced sodium appetite. Gene set enrichment analysis in hypothalami of mice with sodium appetite showed significant enrichment of gene sets previously linked to addiction (opiates and cocaine). This finding of concerted gene regulation was attenuated on gratification with perplexingly rapid kinetics of only 10 min, anteceding significant absorption of salt from the gut. Salt appetite and hedonic liking of salt taste have evolved over 〉100 million y (e.g., being present in Metatheria). Drugs causing pleasure and addiction are comparatively recent and likely reflect usurping of evolutionary ancient systems with high survival value by the gratification of contemporary hedonic indulgences. Our findings outline a molecular logic for instinctive behavior encoded by the brain with possible important translational–medical implications.