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DOI10.1073/PNAS.2005745117
JMJD5 couples with CDK9 to release the paused RNA polymerase II
Liu H.; Ramachandran S.; Fong N.; Phang T.; Lee S.; Parsa P.; Liu X.; Harmacek L.; Danhorn T.; Song T.; Oh S.; Zhang Q.; Chen Z.; Zhang Q.; Tu T.-H.; Happoldt C.; O'Conner B.; Janknecht R.; Li C.-Y.; Marrack P.; Kappler J.; Leach S.; Zhang G.
发表日期2020
ISSN0027-8424
起始页码19888
结束页码19895
卷号117期号:33
英文摘要More than 30% of genes in higher eukaryotes are regulated by RNA polymerase II (Pol II) promoter proximal pausing. Pausing is released by the positive transcription elongation factor complex (P-TEFb). However, the exact mechanism by which this occurs and whether phosphorylation of the carboxyl-terminal domain of Pol II is involved in the process remains unknown. We previously reported that JMJD5 could generate tailless nucleosomes at position +1 from transcription start sites (TSS), thus perhaps enable progression of Pol II. Here we find that knockout of JMJD5 leads to accumulation of nucleosomes at position +1. Absence of JMJD5 also results in loss of or lowered transcription of a large number of genes. Interestingly, we found that phosphorylation, by CDK9, of Ser2 within two neighboring heptad repeats in the carboxyl-terminal domain of Pol II, together with phosphorylation of Ser5 within the second repeat, HR-Ser2p (1, 2)-Ser5p (2) for short, allows Pol II to bind JMJD5 via engagement of the N-terminal domain of JMJD5. We suggest that these events bring JMJD5 near the nucleosome at position +1, thus allowing JMJD5 to clip histones on this nucleosome, a phenomenon that may contribute to release of Pol II pausing. © 2020 National Academy of Sciences. All rights reserved.
语种英语
scopus关键词cyclin dependent kinase 9; membrane protein; protein JMJD5; RNA polymerase II; unclassified drug; CDK9 protein, human; cyclin dependent kinase 9; histone demethylase; KDM8 protein, human; positive transcription elongation factor b; protein binding; RNA polymerase II; animal cell; animal tissue; Article; binding affinity; carboxy terminal sequence; chromatin immunoprecipitation; controlled study; embryo; genetic transcription; human; human cell; male; molecular docking; molecular weight; mouse; nonhuman; nucleosome; priority journal; promoter region; protein analysis; protein binding; protein domain; protein expression; protein folding; protein function; protein phosphorylation; protein protein interaction; transcription initiation site; transcription regulation; chemistry; genetic transcription; genetics; metabolism; phosphorylation; tumor cell line; Cell Line, Tumor; Cyclin-Dependent Kinase 9; Histone Demethylases; Humans; Nucleosomes; Phosphorylation; Positive Transcriptional Elongation Factor B; Promoter Regions, Genetic; Protein Binding; Protein Domains; RNA Polymerase II; Transcription, Genetic
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/160248
作者单位Liu, H., Department of Biomedical Research, National Jewish Health, Denver, CO 80206, United States, Department of Immunology and Microbiology, School of Medicine, University of Colorado Denver, Aurora, CO 80216, United States; Ramachandran, S., RNA Bioscience Initiative, Department of Genetics and Biochemistry, School of Medicine, University of Colorado Denver, Aurora, CO 80216, United States; Fong, N., RNA Bioscience Initiative, Department of Genetics and Biochemistry, School of Medicine, University of Colorado Denver, Aurora, CO 80216, United States; Phang, T., Department of Biostatistics and Informatics, School of Medicine, University of Colorado Denver, Aurora, CO 80216, United States; Lee, S., Department of Biomedical Research, National Jewish Health, Denver, CO 80206, United States, Department of Immunology and Microbiology, School of Medicine, University of Colorado Denver, Aurora, CO 80216, United States; Parsa, P., NanoTemper Technologies, Inc., South San Francisco, CA 94080, United Stat...
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GB/T 7714
Liu H.,Ramachandran S.,Fong N.,et al. JMJD5 couples with CDK9 to release the paused RNA polymerase II[J],2020,117(33).
APA Liu H..,Ramachandran S..,Fong N..,Phang T..,Lee S..,...&Zhang G..(2020).JMJD5 couples with CDK9 to release the paused RNA polymerase II.Proceedings of the National Academy of Sciences of the United States of America,117(33).
MLA Liu H.,et al."JMJD5 couples with CDK9 to release the paused RNA polymerase II".Proceedings of the National Academy of Sciences of the United States of America 117.33(2020).
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