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

查看全文 作　　者：Sue [1]Yu;Jia [2]Li;Guanxu [3]Ji;Zhen Long [1]Ng;Jiamin [1]Siew;Wan Ning [1]Lo;Ying [4]Ye;Yuan Yuan [1]Chew;Yun Chau [1]Long;Wensheng [4]Zhang;Ernesto [5]Guccione;Yuin Han [5]Loh;Zhi-Hong [3]Jiang;Henry [2]Yang;Qiang [1,3]Wu

机构地区：[1]Department of Biochemistry,Yong Loo Lin School of Medicine,National University of Singapore,Singapore 117597,Singapore;[2]Cancer Science Institute of Singapore,Centre for Translational Medicine,Singapore 117599,Singapore;[3]The State Key Laboratory of Quality Research in Chinese Medicine,Macao University of Science and Technology,Macao Special Administrative Region 999078,China;[4]Cam-Su Genomic Resource Center,Soochow University,Suzhou 215123,China;[5]Institute of Molecular and Cell Biology,Singapore 138673,Singapore

出　　处：《Genomics, Proteomics & Bioinformatics》索引2022年第20卷第1期,共19页

基　　金：supported by Singapore National Medical Research Council(Grant No.CBRG14nov065);the Macao Science and Technology Development Fund,China(Grant No.FDCT-18-033-SKL-016A)。 摘　　要：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 PolⅡ(RNA PolⅡSer2P),and Ser5-phosphorylated RNA PolⅡ(RNA PolⅡSer5 P).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 PolⅡSer2P and Ser5P. 关键词：Npac PLURIPOTENCY REPROGRAMMING Histone H3K36me3 Transcriptional elongation

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

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