An HDAC2-TET1 switch at distinct chromatin regions significantly promotes the maturation of pre-iPS to iPS cells

The maturation of induced pluripotent stem cells (iPS) is one of the limiting steps of somatic cell reprogramming, but the underlying mechanism is largely unknown. Here, we reported that knockdown of histone deacetylase 2 (HDAC2) specifically promoted the maturation of iPS cells. Further studies sho...

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Main Authors: Wei, Tingyi, Chen, Wen, Wang, Xiukun, Zhang, Man, Chen, Jiayu, Zhu, Songcheng, Chen, Long, Yang, Dandan, Wang, Guiying, Jia, Wenwen, Yu, Yangyang, Duan, Tao, Wu, Minjuan, Liu, Houqi, Gao, Shaorong, Kang, Jiuhong
Format: Online
Language:English
Published: Oxford University Press 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4477660/
id pubmed-4477660
recordtype oai_dc
spelling pubmed-44776602015-06-29 An HDAC2-TET1 switch at distinct chromatin regions significantly promotes the maturation of pre-iPS to iPS cells Wei, Tingyi Chen, Wen Wang, Xiukun Zhang, Man Chen, Jiayu Zhu, Songcheng Chen, Long Yang, Dandan Wang, Guiying Jia, Wenwen Yu, Yangyang Duan, Tao Wu, Minjuan Liu, Houqi Gao, Shaorong Kang, Jiuhong Gene regulation, Chromatin and Epigenetics The maturation of induced pluripotent stem cells (iPS) is one of the limiting steps of somatic cell reprogramming, but the underlying mechanism is largely unknown. Here, we reported that knockdown of histone deacetylase 2 (HDAC2) specifically promoted the maturation of iPS cells. Further studies showed that HDAC2 knockdown significantly increased histone acetylation, facilitated TET1 binding and DNA demethylation at the promoters of iPS cell maturation-related genes during the transition of pre-iPS cells to a fully reprogrammed state. We also found that HDAC2 competed with TET1 in the binding of the RbAp46 protein at the promoters of maturation genes and knockdown of TET1 markedly prevented the activation of these genes. Collectively, our data not only demonstrated a novel intrinsic mechanism that the HDAC2-TET1 switch critically regulates iPS cell maturation, but also revealed an underlying mechanism of the interplay between histone acetylation and DNA demethylation in gene regulation. Oxford University Press 2015-06-23 2015-05-01 /pmc/articles/PMC4477660/ /pubmed/25934799 http://dx.doi.org/10.1093/nar/gkv430 Text en © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Wei, Tingyi
Chen, Wen
Wang, Xiukun
Zhang, Man
Chen, Jiayu
Zhu, Songcheng
Chen, Long
Yang, Dandan
Wang, Guiying
Jia, Wenwen
Yu, Yangyang
Duan, Tao
Wu, Minjuan
Liu, Houqi
Gao, Shaorong
Kang, Jiuhong
spellingShingle Wei, Tingyi
Chen, Wen
Wang, Xiukun
Zhang, Man
Chen, Jiayu
Zhu, Songcheng
Chen, Long
Yang, Dandan
Wang, Guiying
Jia, Wenwen
Yu, Yangyang
Duan, Tao
Wu, Minjuan
Liu, Houqi
Gao, Shaorong
Kang, Jiuhong
An HDAC2-TET1 switch at distinct chromatin regions significantly promotes the maturation of pre-iPS to iPS cells
author_facet Wei, Tingyi
Chen, Wen
Wang, Xiukun
Zhang, Man
Chen, Jiayu
Zhu, Songcheng
Chen, Long
Yang, Dandan
Wang, Guiying
Jia, Wenwen
Yu, Yangyang
Duan, Tao
Wu, Minjuan
Liu, Houqi
Gao, Shaorong
Kang, Jiuhong
author_sort Wei, Tingyi
title An HDAC2-TET1 switch at distinct chromatin regions significantly promotes the maturation of pre-iPS to iPS cells
title_short An HDAC2-TET1 switch at distinct chromatin regions significantly promotes the maturation of pre-iPS to iPS cells
title_full An HDAC2-TET1 switch at distinct chromatin regions significantly promotes the maturation of pre-iPS to iPS cells
title_fullStr An HDAC2-TET1 switch at distinct chromatin regions significantly promotes the maturation of pre-iPS to iPS cells
title_full_unstemmed An HDAC2-TET1 switch at distinct chromatin regions significantly promotes the maturation of pre-iPS to iPS cells
title_sort hdac2-tet1 switch at distinct chromatin regions significantly promotes the maturation of pre-ips to ips cells
description The maturation of induced pluripotent stem cells (iPS) is one of the limiting steps of somatic cell reprogramming, but the underlying mechanism is largely unknown. Here, we reported that knockdown of histone deacetylase 2 (HDAC2) specifically promoted the maturation of iPS cells. Further studies showed that HDAC2 knockdown significantly increased histone acetylation, facilitated TET1 binding and DNA demethylation at the promoters of iPS cell maturation-related genes during the transition of pre-iPS cells to a fully reprogrammed state. We also found that HDAC2 competed with TET1 in the binding of the RbAp46 protein at the promoters of maturation genes and knockdown of TET1 markedly prevented the activation of these genes. Collectively, our data not only demonstrated a novel intrinsic mechanism that the HDAC2-TET1 switch critically regulates iPS cell maturation, but also revealed an underlying mechanism of the interplay between histone acetylation and DNA demethylation in gene regulation.
publisher Oxford University Press
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4477660/
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