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  • 1
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    Deconvolution of cell-cycle transcription program [Systems Biology] (2013)
    National Academy of Sciences
    Details
    Publication Date: 2013-03-06
    Description: Due to cell-to-cell variability and asymmetric cell division, cells in a synchronized population lose synchrony over time. As a result, time-series measurements from synchronized cell populations do not reflect the underlying dynamics of cell-cycle processes. Here, we present a branching process deconvolution algorithm that learns a more accurate view of...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 2
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    Global control of cell-cycle transcription by coupled CDK and network oscillators (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-05-09
    Description: A significant fraction of the Saccharomyces cerevisiae genome is transcribed periodically during the cell division cycle, indicating that properly timed gene expression is important for regulating cell-cycle events. Genomic analyses of the localization and expression dynamics of transcription factors suggest that a network of sequentially expressed transcription factors could control the temporal programme of transcription during the cell cycle. However, directed studies interrogating small numbers of genes indicate that their periodic transcription is governed by the activity of cyclin-dependent kinases (CDKs). To determine the extent to which the global cell-cycle transcription programme is controlled by cyclin-CDK complexes, we examined genome-wide transcription dynamics in budding yeast mutant cells that do not express S-phase and mitotic cyclins. Here we show that a significant fraction of periodic genes are aberrantly expressed in the cyclin mutant. Although cells lacking cyclins are blocked at the G1/S border, nearly 70% of periodic genes continued to be expressed periodically and on schedule. Our findings reveal that although CDKs have a function in the regulation of cell-cycle transcription, they are not solely responsible for establishing the global periodic transcription programme. We propose that periodic transcription is an emergent property of a transcription factor network that can function as a cell-cycle oscillator independently of, and in tandem with, the CDK oscillator.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2736871/" 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/PMC2736871/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Orlando, David A -- Lin, Charles Y -- Bernard, Allister -- Wang, Jean Y -- Socolar, Joshua E S -- Iversen, Edwin S -- Hartemink, Alexander J -- Haase, Steven B -- P50 GM081883/GM/NIGMS NIH HHS/ -- P50 GM081883-020001/GM/NIGMS NIH HHS/ -- P50 GM081883-030001/GM/NIGMS NIH HHS/ -- England -- Nature. 2008 Jun 12;453(7197):944-7. doi: 10.1038/nature06955. Epub 2008 May 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Duke University, Durham, North Carolina 27708, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18463633" target="_blank"〉PubMed〈/a〉
    Keywords: Biological Clocks/*physiology ; Cell Cycle/*genetics ; Cyclin-Dependent Kinases/genetics/*metabolism ; Cyclins/genetics/metabolism ; G1 Phase ; *Gene Expression Regulation, Fungal ; Mutation/genetics ; Periodicity ; S Phase ; Saccharomyces cerevisiae/*cytology/*genetics ; Time Factors ; *Transcription, Genetic
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 3
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    A high-resolution root spatiotemporal map reveals dominant expression patterns (2007)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2007-11-03
    Description: Transcriptional programs that regulate development are exquisitely controlled in space and time. Elucidating these programs that underlie development is essential to understanding the acquisition of cell and tissue identity. We present microarray expression profiles of a high-resolution set of developmental time points within a single Arabidopsis root and a comprehensive map of nearly all root cell types. These cell type-specific transcriptional signatures often predict previously unknown cellular functions. A computational pipeline identified dominant expression patterns that demonstrate transcriptional similarity between disparate cell types. Dominant expression patterns along the root's longitudinal axis do not strictly correlate with previously defined developmental zones, and in many cases, we observed expression fluctuation along this axis. Both robust co-regulation of gene expression and potential phasing of gene expression were identified between individual roots. Methods that combine these profiles demonstrate transcriptionally rich and complex programs that define Arabidopsis root development in both space and time.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brady, Siobhan M -- Orlando, David A -- Lee, Ji-Young -- Wang, Jean Y -- Koch, Jeremy -- Dinneny, Jose R -- Mace, Daniel -- Ohler, Uwe -- Benfey, Philip N -- New York, N.Y. -- Science. 2007 Nov 2;318(5851):801-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Duke University, Durham, NC 27708, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17975066" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/cytology/*genetics/growth & development ; Gene Expression Profiling ; *Gene Expression Regulation, Developmental ; *Gene Expression Regulation, Plant ; Green Fluorescent Proteins ; Oligonucleotide Array Sequence Analysis ; Plant Roots/cytology/*genetics/growth & development
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 4
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    The histone methyltransferase SETDB1 is recurrently amplified in melanoma and accelerates its onset (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-03-25
    Description: The most common mutation in human melanoma, BRAF(V600E), activates the serine/threonine kinase BRAF and causes excessive activity in the mitogen-activated protein kinase pathway. BRAF(V600E) mutations are also present in benign melanocytic naevi, highlighting the importance of additional genetic alterations in the genesis of malignant tumours. Such changes include recurrent copy number variations that result in the amplification of oncogenes. For certain amplifications, the large number of genes in the interval has precluded an understanding of the cooperating oncogenic events. Here we have used a zebrafish melanoma model to test genes in a recurrently amplified region of chromosome 1 for the ability to cooperate with BRAF(V600E) and accelerate melanoma. SETDB1, an enzyme that methylates histone H3 on lysine 9 (H3K9), was found to accelerate melanoma formation significantly in zebrafish. Chromatin immunoprecipitation coupled with massively parallel DNA sequencing and gene expression analyses uncovered genes, including HOX genes, that are transcriptionally dysregulated in response to increased levels of SETDB1. Our studies establish SETDB1 as an oncogene in melanoma and underscore the role of chromatin factors in regulating tumorigenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348545/" 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/PMC3348545/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ceol, Craig J -- Houvras, Yariv -- Jane-Valbuena, Judit -- Bilodeau, Steve -- Orlando, David A -- Battisti, Valentine -- Fritsch, Lauriane -- Lin, William M -- Hollmann, Travis J -- Ferre, Fabrizio -- Bourque, Caitlin -- Burke, Christopher J -- Turner, Laura -- Uong, Audrey -- Johnson, Laura A -- Beroukhim, Rameen -- Mermel, Craig H -- Loda, Massimo -- Ait-Si-Ali, Slimane -- Garraway, Levi A -- Young, Richard A -- Zon, Leonard I -- CA103846/CA/NCI NIH HHS/ -- CA146455/CA/NCI NIH HHS/ -- DK055381/DK/NIDDK NIH HHS/ -- HG002668/HG/NHGRI NIH HHS/ -- K08 DK075432/DK/NIDDK NIH HHS/ -- K08 DK075432-04/DK/NIDDK NIH HHS/ -- K08DK075432-04/DK/NIDDK NIH HHS/ -- K99AR056899-02/AR/NIAMS NIH HHS/ -- R00 AR056899/AR/NIAMS NIH HHS/ -- R00 AR056899-02/AR/NIAMS NIH HHS/ -- R01 CA103846/CA/NCI NIH HHS/ -- R01 CA103846-09/CA/NCI NIH HHS/ -- R01 CA146445/CA/NCI NIH HHS/ -- R01 CA146445-03/CA/NCI NIH HHS/ -- R01 HG002668/HG/NHGRI NIH HHS/ -- R01 HG002668-08/HG/NHGRI NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- Canadian Institutes of Health Research/Canada -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Mar 24;471(7339):513-7. doi: 10.1038/nature09806.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stem Cell Program and Hematology/Oncology, Children's Hospital Boston, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21430779" target="_blank"〉PubMed〈/a〉
    Keywords: Age of Onset ; Amino Acid Substitution ; Animals ; Animals, Genetically Modified ; Cell Transformation, Neoplastic/genetics ; Chromatin Immunoprecipitation ; Chromosomes, Human, Pair 1/genetics ; DNA Copy Number Variations/*genetics ; Disease Models, Animal ; Gene Amplification/*genetics ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic/genetics ; Genes, Homeobox/genetics ; Histone-Lysine N-Methyltransferase/*genetics/metabolism ; Humans ; Melanocytes/cytology/enzymology/metabolism/pathology ; Melanoma/enzymology/*genetics/*pathology ; Nevus/enzymology ; Oncogenes/genetics ; Protein Methyltransferases/*genetics/*metabolism ; Proto-Oncogene Proteins B-raf/chemistry/genetics/metabolism ; Zebrafish/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 5
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    Enhancer decommissioning by LSD1 during embryonic stem cell differentiation (2012)
    Nature Publishing Group (NPG)
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    Publication Date: 2012-02-03
    Description: Transcription factors and chromatin modifiers are important in the programming and reprogramming of cellular states during development. Transcription factors bind to enhancer elements and recruit coactivators and chromatin-modifying enzymes to facilitate transcription initiation. During differentiation a subset of these enhancers must be silenced, but the mechanisms underlying enhancer silencing are poorly understood. Here we show that the histone demethylase lysine-specific demethylase 1 (LSD1; ref. 5), which demethylates histone H3 on Lys 4 or Lys 9 (H3K4/K9), is essential in decommissioning enhancers during the differentiation of mouse embryonic stem cells (ESCs). LSD1 occupies enhancers of active genes that are critical for control of the state of ESCs. However, LSD1 is not essential for the maintenance of ESC identity. Instead, ESCs lacking LSD1 activity fail to differentiate fully, and ESC-specific enhancers fail to undergo the histone demethylation events associated with differentiation. At active enhancers, LSD1 is a component of the NuRD (nucleosome remodelling and histone deacetylase) complex, which contains additional subunits that are necessary for ESC differentiation. We propose that the LSD1-NuRD complex decommissions enhancers of the pluripotency program during differentiation, which is essential for the complete shutdown of the ESC gene expression program and the transition to new cell states.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4144424/" 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/PMC4144424/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Whyte, Warren A -- Bilodeau, Steve -- Orlando, David A -- Hoke, Heather A -- Frampton, Garrett M -- Foster, Charles T -- Cowley, Shaun M -- Young, Richard A -- G0600135/Medical Research Council/United Kingdom -- HG002668/HG/NHGRI NIH HHS/ -- NS055923/NS/NINDS NIH HHS/ -- P01 NS055923/NS/NINDS NIH HHS/ -- R01 HG002668/HG/NHGRI NIH HHS/ -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2012 Feb 1;482(7384):221-5. doi: 10.1038/nature10805.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22297846" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation/*genetics ; Embryonic Stem Cells/*cytology/*metabolism ; Enhancer Elements, Genetic/*genetics ; Fibroblasts ; *Gene Silencing ; Histone Demethylases ; Mi-2 Nucleosome Remodeling and Deacetylase Complex/metabolism ; Mice ; Oxidoreductases, N-Demethylating/antagonists & inhibitors/*metabolism ; Promoter Regions, Genetic/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 6
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    Mediator and cohesin connect gene expression and chromatin architecture (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-08-20
    Description: Transcription factors control cell-specific gene expression programs through interactions with diverse coactivators and the transcription apparatus. Gene activation may involve DNA loop formation between enhancer-bound transcription factors and the transcription apparatus at the core promoter, but this process is not well understood. Here we report that mediator and cohesin physically and functionally connect the enhancers and core promoters of active genes in murine embryonic stem cells. Mediator, a transcriptional coactivator, forms a complex with cohesin, which can form rings that connect two DNA segments. The cohesin-loading factor Nipbl is associated with mediator-cohesin complexes, providing a means to load cohesin at promoters. DNA looping is observed between the enhancers and promoters occupied by mediator and cohesin. Mediator and cohesin co-occupy different promoters in different cells, thus generating cell-type-specific DNA loops linked to the gene expression program of each cell.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2953795/" 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/PMC2953795/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kagey, Michael H -- Newman, Jamie J -- Bilodeau, Steve -- Zhan, Ye -- Orlando, David A -- van Berkum, Nynke L -- Ebmeier, Christopher C -- Goossens, Jesse -- Rahl, Peter B -- Levine, Stuart S -- Taatjes, Dylan J -- Dekker, Job -- Young, Richard A -- HG002668/HG/NHGRI NIH HHS/ -- HG003143/HG/NHGRI NIH HHS/ -- R01 HG002668/HG/NHGRI NIH HHS/ -- R01 HG002668-07/HG/NHGRI NIH HHS/ -- R01 HG003143/HG/NHGRI NIH HHS/ -- R01 HG003143-06/HG/NHGRI NIH HHS/ -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2010 Sep 23;467(7314):430-5. doi: 10.1038/nature09380. Epub 2010 Aug 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20720539" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Cycle Proteins/genetics/*metabolism ; Cells, Cultured ; Chromatin/chemistry/*genetics/*metabolism ; Chromatin Assembly and Disassembly/*genetics ; Chromosomal Proteins, Non-Histone/genetics/*metabolism ; DNA/chemistry/genetics/metabolism ; Embryonic Stem Cells/cytology/*metabolism ; Enhancer Elements, Genetic/genetics ; Fibroblasts ; Gene Expression Regulation/*genetics ; Mediator Complex/genetics/*metabolism ; Mice ; Nucleic Acid Conformation ; Organ Specificity ; Promoter Regions, Genetic/genetics ; Protein Binding
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 7
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    Divergent transcription of long noncoding RNA/mRNA gene pairs in embryonic stem cells (2013)
    National Academy of Sciences
    Details
    Publication Date: 2013-02-04
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 8
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    Branching process deconvolution algorithm reveals a detailed cell-cycle transcription program (2013)
    National Academy of Sciences
    Details
    Publication Date: 2013-02-06
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 9
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    Divergent transcription of lncRNA/mRNA gene pairs [Developmental Biology] (2013)
    National Academy of Sciences
    Details
    Publication Date: 2013-02-20
    Description: Many long noncoding RNA (lncRNA) species have been identified in mammalian cells, but the genomic origin and regulation of these molecules in individual cell types is poorly understood. We have generated catalogs of lncRNA species expressed in human and murine embryonic stem cells and mapped their genomic origin. A surprisingly...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 10
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    Reconstructing spatiotemporal gene expression data from partial observations (2009)
    Oxford University Press
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    Publication Date: 2009-07-16
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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