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ZFP281 coordinates DNMT3 and TET1 for transcriptional and epigenetic control in pluripotent state transitions

The progression from naive through formative to primed in vitro pluripotent stem cell states recapitulates the development of the epiblast in vivo during the peri-implantation period of mammalian development. Activation of the de novo DNA methyltransferases and reorganization of transcriptional and...

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Autores principales: Huang, Xin, Balmer, Sophie, Lyu, Cong, Xiang, Yunlong, Malik, Vikas, Wang, Hailin, Zhang, Yu, Xie, Wei, Hadjantonakis, Anna-Katerina, Zhou, Hongwei, Wang, Jianlong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10055359/
https://www.ncbi.nlm.nih.gov/pubmed/36993548
http://dx.doi.org/10.1101/2023.03.24.534143
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author Huang, Xin
Balmer, Sophie
Lyu, Cong
Xiang, Yunlong
Malik, Vikas
Wang, Hailin
Zhang, Yu
Xie, Wei
Hadjantonakis, Anna-Katerina
Zhou, Hongwei
Wang, Jianlong
author_facet Huang, Xin
Balmer, Sophie
Lyu, Cong
Xiang, Yunlong
Malik, Vikas
Wang, Hailin
Zhang, Yu
Xie, Wei
Hadjantonakis, Anna-Katerina
Zhou, Hongwei
Wang, Jianlong
author_sort Huang, Xin
collection PubMed
description The progression from naive through formative to primed in vitro pluripotent stem cell states recapitulates the development of the epiblast in vivo during the peri-implantation period of mammalian development. Activation of the de novo DNA methyltransferases and reorganization of transcriptional and epigenetic landscapes are key events occurring during these pluripotent state transitions. However, the upstream regulators that coordinate these events are relatively underexplored. Here, using Zfp281 knockout mouse and degron knock-in cell models, we uncover the direct transcriptional activation of Dnmt3a/3b by ZFP281 in pluripotent stem cells. Chromatin co-occupancy of ZFP281 and DNA hydroxylase TET1, dependent on the formation of R loops in ZFP281-targeted gene promoters, undergoes a “high-low-high” bimodal pattern regulating dynamic DNA methylation and gene expression during the naïive-formative-primed transitions. ZFP281 also safeguards DNA methylation in maintaining primed pluripotency. Our study demonstrates a previously unappreciated role for ZFP281 in coordinating DNMT3A/3B and TET1 functions to promote pluripotent state transitions.
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spelling pubmed-100553592023-03-30 ZFP281 coordinates DNMT3 and TET1 for transcriptional and epigenetic control in pluripotent state transitions Huang, Xin Balmer, Sophie Lyu, Cong Xiang, Yunlong Malik, Vikas Wang, Hailin Zhang, Yu Xie, Wei Hadjantonakis, Anna-Katerina Zhou, Hongwei Wang, Jianlong bioRxiv Article The progression from naive through formative to primed in vitro pluripotent stem cell states recapitulates the development of the epiblast in vivo during the peri-implantation period of mammalian development. Activation of the de novo DNA methyltransferases and reorganization of transcriptional and epigenetic landscapes are key events occurring during these pluripotent state transitions. However, the upstream regulators that coordinate these events are relatively underexplored. Here, using Zfp281 knockout mouse and degron knock-in cell models, we uncover the direct transcriptional activation of Dnmt3a/3b by ZFP281 in pluripotent stem cells. Chromatin co-occupancy of ZFP281 and DNA hydroxylase TET1, dependent on the formation of R loops in ZFP281-targeted gene promoters, undergoes a “high-low-high” bimodal pattern regulating dynamic DNA methylation and gene expression during the naïive-formative-primed transitions. ZFP281 also safeguards DNA methylation in maintaining primed pluripotency. Our study demonstrates a previously unappreciated role for ZFP281 in coordinating DNMT3A/3B and TET1 functions to promote pluripotent state transitions. Cold Spring Harbor Laboratory 2023-03-25 /pmc/articles/PMC10055359/ /pubmed/36993548 http://dx.doi.org/10.1101/2023.03.24.534143 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Huang, Xin
Balmer, Sophie
Lyu, Cong
Xiang, Yunlong
Malik, Vikas
Wang, Hailin
Zhang, Yu
Xie, Wei
Hadjantonakis, Anna-Katerina
Zhou, Hongwei
Wang, Jianlong
ZFP281 coordinates DNMT3 and TET1 for transcriptional and epigenetic control in pluripotent state transitions
title ZFP281 coordinates DNMT3 and TET1 for transcriptional and epigenetic control in pluripotent state transitions
title_full ZFP281 coordinates DNMT3 and TET1 for transcriptional and epigenetic control in pluripotent state transitions
title_fullStr ZFP281 coordinates DNMT3 and TET1 for transcriptional and epigenetic control in pluripotent state transitions
title_full_unstemmed ZFP281 coordinates DNMT3 and TET1 for transcriptional and epigenetic control in pluripotent state transitions
title_short ZFP281 coordinates DNMT3 and TET1 for transcriptional and epigenetic control in pluripotent state transitions
title_sort zfp281 coordinates dnmt3 and tet1 for transcriptional and epigenetic control in pluripotent state transitions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10055359/
https://www.ncbi.nlm.nih.gov/pubmed/36993548
http://dx.doi.org/10.1101/2023.03.24.534143
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