WFRF:(Zhang Mingzhi)
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Super-enhancers conserved within placental mammals maintain stem cell pluripotency
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- Zhang, Juqing (författare)
- Northwest A&F Univ, Coll Vet Med, Shaanxi Ctr Stem Cells Engn & Technol, Yangling 712100, Shaanxi, Peoples R China.
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- Zhou, Yaqi (författare)
- Northwest A&F Univ, Coll Life Sci, Yangling 712100, Shaanxi, Peoples R China.
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- Yue, Wei (författare)
- Northwest A&F Univ, Coll Vet Med, Shaanxi Ctr Stem Cells Engn & Technol, Yangling 712100, Shaanxi, Peoples R China.
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- Northwest A&F Univ, Coll Vet Med, Shaanxi Ctr Stem Cells Engn & Technol, Yangling 712100, Shaanxi, Peoples R China Northwest A&F Univ, Coll Life Sci, Yangling 712100, Shaanxi, Peoples R China. (creator_code:org_t)
- 2022-09-26
- 2022
- Engelska.
- Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 119:40
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- Despite pluripotent stem cells sharing key transcription factors, their maintenance involves distinct genetic inputs. Emerging evidence suggests that super-enhancers (SEs) can function as master regulatory hubs to control cell identity and pluripotency in humans and mice. However, whether pluripotency-associated SEs share an evolutionary origin in mammals remains elusive. Here, we performed comprehensive comparative epigenomic and transcription factor binding analyses among pigs, humans, and mice to identify pluripotency-associated SEs. Like typical enhancers, SEs displayed rapid evolu-tion in mammals. We showed that BRD4 is an essential and conserved activator for mammalian pluripotency-associated SEs. Comparative motif enrichment analysis revealed 30 shared transcription factor binding motifs among the three species. The majority of transcriptional factors that bind to identified motifs are known regulators associated with pluripotency. Further, we discovered three pluripotency-associated SEs (SE-SOX2, SE-PIM1, and SE-FGFR1) that displayed remarkable conservation in pla-cental mammals and were sufficient to drive reporter gene expression in a pluripotency-dependent manner. Disruption of these conserved SEs through the CRISPR-Cas9 approach severely impaired stem cell pluripotency. Our study provides insights into the understanding of conserved regulatory mechanisms underlying the maintenance of plu-ripotency as well as species-specific modulation of the pluripotency-associated regula-tory networks in mammals.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- pluripotency
- super-enhancer
- evolution
- pigs
- BRD4
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- Zhang, Juqing
- Zhou, Yaqi
- Yue, Wei
- Zhu, Zhenshuo
- Wu, Xiaolong
- Yu, Shuai
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- Shen, Qiaoyan
- Pan, Qin
- Xu, Wenjing
- Zhang, Rui
- Wu, Xiaojie
- Li, Xinmei
- Li, Yayu
- Li, Yunxiang
- Wang, Yu
- Peng, Sha
- Zhang, Shiqiang
- Lei, Anmin
- Ding, Xinbao
- Yang, Fan
- Chen, Xingqi
- Li, Na
- Liao, Mingzhi
- Warg, Wei
- Hua, Jinlian
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