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KLF4 inhibits early neural differentiation of ESCs by coordinating specific 3D chromatin structure

Neural differentiation of embryonic stem cells (ESCs) requires precisely orchestrated gene regulation, a process governed in part by changes in 3D chromatin structure. How these changes regulate gene expression in this context remains unclear. In this study, we observed enrichment of the transcripti...

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Autores principales: Bi, Jinfang, Wang, Wenbin, Zhang, Meng, Zhang, Baoying, Liu, Man, Su, Guangsong, Chen, Fuquan, Chen, Bohan, Shi, Tengfei, Zheng, Yaoqiang, Zhao, Xueyuan, Zhao, Zhongfang, Shi, Jiandang, Li, Peng, Zhang, Lei, Lu, Wange
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9757050/
https://www.ncbi.nlm.nih.gov/pubmed/36477888
http://dx.doi.org/10.1093/nar/gkac1118
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author Bi, Jinfang
Wang, Wenbin
Zhang, Meng
Zhang, Baoying
Liu, Man
Su, Guangsong
Chen, Fuquan
Chen, Bohan
Shi, Tengfei
Zheng, Yaoqiang
Zhao, Xueyuan
Zhao, Zhongfang
Shi, Jiandang
Li, Peng
Zhang, Lei
Lu, Wange
author_facet Bi, Jinfang
Wang, Wenbin
Zhang, Meng
Zhang, Baoying
Liu, Man
Su, Guangsong
Chen, Fuquan
Chen, Bohan
Shi, Tengfei
Zheng, Yaoqiang
Zhao, Xueyuan
Zhao, Zhongfang
Shi, Jiandang
Li, Peng
Zhang, Lei
Lu, Wange
author_sort Bi, Jinfang
collection PubMed
description Neural differentiation of embryonic stem cells (ESCs) requires precisely orchestrated gene regulation, a process governed in part by changes in 3D chromatin structure. How these changes regulate gene expression in this context remains unclear. In this study, we observed enrichment of the transcription factor KLF4 at some poised or closed enhancers at TSS-linked regions of genes associated with neural differentiation. Combination analysis of ChIP, HiChIP and RNA-seq data indicated that KLF4 loss in ESCs induced changes in 3D chromatin structure, including increased chromatin interaction loops between neural differentiation-associated genes and active enhancers, leading to upregulated expression of neural differentiation-associated genes and therefore early neural differentiation. This study suggests KLF4 inhibits early neural differentiation by regulation of 3D chromatin structure, which is a new mechanism of early neural differentiation.
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spelling pubmed-97570502022-12-19 KLF4 inhibits early neural differentiation of ESCs by coordinating specific 3D chromatin structure Bi, Jinfang Wang, Wenbin Zhang, Meng Zhang, Baoying Liu, Man Su, Guangsong Chen, Fuquan Chen, Bohan Shi, Tengfei Zheng, Yaoqiang Zhao, Xueyuan Zhao, Zhongfang Shi, Jiandang Li, Peng Zhang, Lei Lu, Wange Nucleic Acids Res Gene regulation, Chromatin and Epigenetics Neural differentiation of embryonic stem cells (ESCs) requires precisely orchestrated gene regulation, a process governed in part by changes in 3D chromatin structure. How these changes regulate gene expression in this context remains unclear. In this study, we observed enrichment of the transcription factor KLF4 at some poised or closed enhancers at TSS-linked regions of genes associated with neural differentiation. Combination analysis of ChIP, HiChIP and RNA-seq data indicated that KLF4 loss in ESCs induced changes in 3D chromatin structure, including increased chromatin interaction loops between neural differentiation-associated genes and active enhancers, leading to upregulated expression of neural differentiation-associated genes and therefore early neural differentiation. This study suggests KLF4 inhibits early neural differentiation by regulation of 3D chromatin structure, which is a new mechanism of early neural differentiation. Oxford University Press 2022-12-07 /pmc/articles/PMC9757050/ /pubmed/36477888 http://dx.doi.org/10.1093/nar/gkac1118 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Gene regulation, Chromatin and Epigenetics
Bi, Jinfang
Wang, Wenbin
Zhang, Meng
Zhang, Baoying
Liu, Man
Su, Guangsong
Chen, Fuquan
Chen, Bohan
Shi, Tengfei
Zheng, Yaoqiang
Zhao, Xueyuan
Zhao, Zhongfang
Shi, Jiandang
Li, Peng
Zhang, Lei
Lu, Wange
KLF4 inhibits early neural differentiation of ESCs by coordinating specific 3D chromatin structure
title KLF4 inhibits early neural differentiation of ESCs by coordinating specific 3D chromatin structure
title_full KLF4 inhibits early neural differentiation of ESCs by coordinating specific 3D chromatin structure
title_fullStr KLF4 inhibits early neural differentiation of ESCs by coordinating specific 3D chromatin structure
title_full_unstemmed KLF4 inhibits early neural differentiation of ESCs by coordinating specific 3D chromatin structure
title_short KLF4 inhibits early neural differentiation of ESCs by coordinating specific 3D chromatin structure
title_sort klf4 inhibits early neural differentiation of escs by coordinating specific 3d chromatin structure
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9757050/
https://www.ncbi.nlm.nih.gov/pubmed/36477888
http://dx.doi.org/10.1093/nar/gkac1118
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