典型文献
Unveiling E2F4,TEAD1 and AP-1 as regulatory transcription factors of the replicative senescence program by multi-omics analysis
文献摘要：
Senescence,a stable state of growth arrest,affects many physiological and pathophysiological processes,especially aging.Previous work has indicated that transcription factors(TFs)play a role in regulating senescence.However,a systematic study of regulatory TFs during replicative senescence(RS)using multi-omics analysis is still lacking.Here,we generated time-resolved RNA-seq,reduced representation bisulfite sequencing(RRBS)and ATAC-seq datasets during RS of mouse skin fibroblasts,which demonstrated that an enhanced inflammatory response and reduced prolifer-ative capacity were the main characteristics of RS in both the transcriptome and epigenome.Through inte-grative analysis and genetic manipulations,we found that transcription factors E2F4,TEAD1 and AP-1 are key regulators of RS.Overexpression of E2f4 improved cellular proliferative capacity,attenuated SA-β-Gal activity and changed RS-associated differentially methylated sites(DMSs).Moreover,knockdown of Tead1 attenuated SA--p-Gal activity and partially altered the RS-associated transcriptome.In addition,knock-down of Atf3,one member of AP-1 superfamily TFs,reduced Cdkn2a(p1 6)expression in pre-senescent fibroblasts.Taken together,the results of this study identified transcription factors regulating the senes-cence program through multi-omics analysis,providing potential therapeutic targets for anti-aging.
文献关键词：
中图分类号：
作者姓名：
Yuting Wang;Liping Liu;Yifan Song;Xiaojie Yu;Hongkui Deng
作者机构：
School of Basic Medical Sciences,State Key Laboratory of Natural and Biomimetic Drugs,Peking University,Beijing 100191,China;The MOE Key Laboratory of Cell Proliferation and Differentiation,College of Life Sciences,Peking-Tsinghua Center for Life Sciences,Peking University,Beijing 100871,China;State Key Laboratory of Chemical Oncogenomics,School of Chemical Biology and Biotechnology,Peking University Shenzhen Graduate School,Shenzhen 518055,China
文献出处：
引用格式：
[1]Yuting Wang;Liping Liu;Yifan Song;Xiaojie Yu;Hongkui Deng-.Unveiling E2F4,TEAD1 and AP-1 as regulatory transcription factors of the replicative senescence program by multi-omics analysis)[J].蛋白质与细胞,2022(10):742-759
A类：
prolifer,grative,E2f4,DMSs,Cdkn2a
B类：
Unveiling,E2F4,TEAD1,AP,regulatory,transcription,factors,replicative,senescence,program,by,multi,omics,analysis,Senescence,stable,state,growth,arrest,affects,many,pathophysiological,processes,especially,aging,Previous,work,has,indicated,that,TFs,play,role,regulating,However,systematic,study,during,RS,using,still,lacking,Here,generated,resolved,reduced,representation,bisulfite,sequencing,RRBS,ATAC,datasets,mouse,skin,fibroblasts,which,demonstrated,enhanced,inflammatory,response,capacity,were,main,characteristics,both,transcriptome,epigenome,Through,inte,genetic,manipulations,found,are,key,regulators,Overexpression,improved,cellular,proliferative,attenuated,SA,Gal,activity,changed,associated,differentially,methylated,sites,Moreover,knockdown,Tead1,partially,altered,In,addition,Atf3,one,member,superfamily,p1,senescent,Taken,together,results,this,identified,through,providing,potential,therapeutic,targets,anti
AB值：
0.590493
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