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  • 1
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    Transcription regulation through promoter-proximal pausing of RNA polymerase II (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2008-03-29
    Description: Recent work has shown that the RNA polymerase II enzyme pauses at a promoter-proximal site of many genes in Drosophila and mammals. This rate-limiting step occurs after recruitment and initiation of RNA polymerase II at a gene promoter. This stage in early elongation appears to be an important and broadly used target of gene regulation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2833332/" 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/PMC2833332/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Core, Leighton J -- Lis, John T -- R01 GM025232/GM/NIGMS NIH HHS/ -- R01 GM025232-32/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2008 Mar 28;319(5871):1791-2. doi: 10.1126/science.1150843.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18369138" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Drosophila/genetics ; *Gene Expression Regulation ; Humans ; *Promoter Regions, Genetic ; RNA Polymerase II/*metabolism ; RNA Precursors/metabolism ; RNA Processing, Post-Transcriptional ; *Transcription, Genetic
    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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  • 2
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    Nascent RNA sequencing reveals widespread pausing and divergent initiation at human promoters (2008)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2008-12-06
    Description: RNA polymerases are highly regulated molecular machines. We present a method (global run-on sequencing, GRO-seq) that maps the position, amount, and orientation of transcriptionally engaged RNA polymerases genome-wide. In this method, nuclear run-on RNA molecules are subjected to large-scale parallel sequencing and mapped to the genome. We show that peaks of promoter-proximal polymerase reside on approximately 30% of human genes, transcription extends beyond pre-messenger RNA 3' cleavage, and antisense transcription is prevalent. Additionally, most promoters have an engaged polymerase upstream and in an orientation opposite to the annotated gene. This divergent polymerase is associated with active genes but does not elongate effectively beyond the promoter. These results imply that the interplay between polymerases and regulators over broad promoter regions dictates the orientation and efficiency of productive transcription.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2833333/" 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/PMC2833333/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Core, Leighton J -- Waterfall, Joshua J -- Lis, John T -- GM25232/GM/NIGMS NIH HHS/ -- R01 GM025232/GM/NIGMS NIH HHS/ -- R01 GM025232-32/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2008 Dec 19;322(5909):1845-8. doi: 10.1126/science.1162228. Epub 2008 Dec 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19056941" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; CpG Islands ; DNA-Directed RNA Polymerases/*metabolism ; Genome, Human ; Humans ; Nucleosomes/metabolism ; *Promoter Regions, Genetic ; RNA Polymerase II/*metabolism ; RNA, Antisense/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; *Sequence Analysis, RNA ; Transcription Initiation Site ; *Transcription, Genetic
    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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  • 3
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    Coordinated effects of sequence variation on DNA binding, chromatin structure, and transcription (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-10-19
    Description: DNA sequence variation has been associated with quantitative changes in molecular phenotypes such as gene expression, but its impact on chromatin states is poorly characterized. To understand the interplay between chromatin and genetic control of gene regulation, we quantified allelic variability in transcription factor binding, histone modifications, and gene expression within humans. We found abundant allelic specificity in chromatin and extensive local, short-range, and long-range allelic coordination among the studied molecular phenotypes. We observed genetic influence on most of these phenotypes, with histone modifications exhibiting strong context-dependent behavior. Our results implicate transcription factors as primary mediators of sequence-specific regulation of gene expression programs, with histone modifications frequently reflecting the primary regulatory event.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kilpinen, Helena -- Waszak, Sebastian M -- Gschwind, Andreas R -- Raghav, Sunil K -- Witwicki, Robert M -- Orioli, Andrea -- Migliavacca, Eugenia -- Wiederkehr, Michael -- Gutierrez-Arcelus, Maria -- Panousis, Nikolaos I -- Yurovsky, Alisa -- Lappalainen, Tuuli -- Romano-Palumbo, Luciana -- Planchon, Alexandra -- Bielser, Deborah -- Bryois, Julien -- Padioleau, Ismael -- Udin, Gilles -- Thurnheer, Sarah -- Hacker, David -- Core, Leighton J -- Lis, John T -- Hernandez, Nouria -- Reymond, Alexandre -- Deplancke, Bart -- Dermitzakis, Emmanouil T -- GM25232/GM/NIGMS NIH HHS/ -- HG004845/HG/NHGRI NIH HHS/ -- R01 HG004845/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2013 Nov 8;342(6159):744-7. doi: 10.1126/science.1242463. Epub 2013 Oct 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24136355" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Base Sequence/genetics ; Binding Sites/genetics ; Chromatin/chemistry/*metabolism ; DNA/chemistry/*metabolism ; *Gene Expression Regulation ; *Genetic Variation ; Histones/chemistry/metabolism ; Humans ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; 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
    Published by American Association for the Advancement of Science (AAAS)
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  • 4
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    Precise maps of RNA polymerase reveal how promoters direct initiation and pausing (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-02-23
    Description: Transcription regulation occurs frequently through promoter-associated pausing of RNA polymerase II (Pol II). We developed a precision nuclear run-on and sequencing (PRO-seq) assay to map the genome-wide distribution of transcriptionally engaged Pol II at base pair resolution. Pol II accumulates immediately downstream of promoters, at intron-exon junctions that are efficiently used for splicing, and over 3' polyadenylation sites. Focused analyses of promoters reveal that pausing is not fixed relative to initiation sites, nor is it specified directly by the position of a particular core promoter element or the first nucleosome. Core promoter elements function beyond initiation, and when optimally positioned they act collectively to dictate the position and strength of pausing. This "complex interaction" model was tested with insertional mutagenesis of the Drosophila Hsp70 core promoter.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3974810/" 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/PMC3974810/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kwak, Hojoong -- Fuda, Nicholas J -- Core, Leighton J -- Lis, John T -- GM25232/GM/NIGMS NIH HHS/ -- HG004845/HG/NHGRI NIH HHS/ -- R01 GM025232/GM/NIGMS NIH HHS/ -- R01 HG004845/HG/NHGRI NIH HHS/ -- R37 GM025232/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Feb 22;339(6122):950-3. doi: 10.1126/science.1229386.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23430654" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; Base Pairing ; Drosophila Proteins/genetics ; Drosophila melanogaster/*genetics ; Gene Expression Regulation ; Genes, Insect ; Genome, Insect ; HSP70 Heat-Shock Proteins/genetics ; Models, Genetic ; Mutagenesis, Insertional ; Nucleosomes/metabolism ; *Promoter Regions, Genetic ; RNA Polymerase II/*metabolism ; RNA Splice Sites ; *Transcription Initiation, Genetic ; *Transcription, Genetic ; Transgenes
    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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  • 5
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    X chromosome dosage compensation via enhanced transcriptional elongation in Drosophila (2011)
    Nature Publishing Group (NPG)
    Details
    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
    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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