Npac Is A Co-factor of Histone H3K36me3 and Regulates Transcriptional Elongation in Mouse Embryonic Stem Cells.

Autor:	Yu S; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore., Li J; Cancer Science Institute of Singapore, Centre for Translational Medicine, Singapore 117599, Singapore., Ji G; The State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau Special Administrative Region 999078, China., Ng ZL; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore., Siew J; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore., Lo WN; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore., Ye Y; Cam-Su Genomic Resource Center, Soochow University, Suzhou 215123, China., Chew YY; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore., Long YC; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore., Zhang W; Cam-Su Genomic Resource Center, Soochow University, Suzhou 215123, China., Guccione E; Institute of Molecular and Cell Biology, Singapore 138673, Singapore., Loh YH; Institute of Molecular and Cell Biology, Singapore 138673, Singapore., Jiang ZH; The State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau Special Administrative Region 999078, China., Yang H; Cancer Science Institute of Singapore, Centre for Translational Medicine, Singapore 117599, Singapore. Electronic address: csiyangh@nus.edu.sg., Wu Q; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; The State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau Special Administrative Region 999078, China. Electronic address: qwu@must.edu.mo.
Jazyk:	angličtina
Zdroj:	Genomics, proteomics & bioinformatics [Genomics Proteomics Bioinformatics] 2022 Feb; Vol. 20 (1), pp. 110-128. Date of Electronic Publication: 2021 Mar 04.
DOI:	10.1016/j.gpb.2020.08.004
Abstrakt:	Chromatin modification contributes to pluripotency maintenance in embryonic stem cells (ESCs). However, the related mechanisms remain obscure. Here, we show that Npac, a "reader" of histone H3 lysine 36 trimethylation (H3K36me3), is required to maintain mouse ESC (mESC) pluripotency since knockdown of Npac causes mESC differentiation. Depletion of Npac in mouse embryonic fibroblasts (MEFs) inhibits reprogramming efficiency. Furthermore, our chromatin immunoprecipitation followed by sequencing (ChIP-seq) results of Npac reveal that Npac co-localizes with histone H3K36me3 in gene bodies of actively transcribed genes in mESCs. Interestingly, we find that Npac interacts with positive transcription elongation factor b (p-TEFb), Ser2-phosphorylated RNA Pol II (RNA Pol II Ser2P), and Ser5-phosphorylated RNA Pol II (RNA Pol II Ser5P). Furthermore, depletion of Npac disrupts transcriptional elongation of the pluripotency genes Nanog and Rif1. Taken together, we propose that Npac is essential for the transcriptional elongation of pluripotency genes by recruiting p-TEFb and interacting with RNA Pol II Ser2P and Ser5P. (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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