ZFP281 controls transcriptional and epigenetic changes promoting mouse pluripotent state transitions via DNMT3 and TET1 Journal Article

   

Authors:	Huang, X.; Balmer, S.; Lyu, C.; Xiang, Y.; Malik, V.; Wang, H.; Zhang, Y.; Cai, B.; Xie, W.; Hadjantonakis, A. K.; Zhou, H.; Wang, J.
Article Title:	ZFP281 controls transcriptional and epigenetic changes promoting mouse pluripotent state transitions via DNMT3 and TET1
Abstract:	The progression from naive through formative to primed in vitro pluripotent stem cell states recapitulates epiblast development in vivo during the peri-implantation period of mouse embryo development. Activation of the de novo DNA methyltransferases and reorganization of transcriptional and epigenetic landscapes are key events that occur during these pluripotent state transitions. However, the upstream regulators that coordinate these events are relatively underexplored. Here, using Zfp281 knockout mouse and degron knockin cell models, we identify the direct transcriptional activation of Dnmt3a/3b by ZFP281 in pluripotent stem cells. Chromatin co-occupancy of ZFP281 and DNA hydroxylase TET1, which is 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 naive-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. © 2023 Elsevier Inc.
Keywords:	dna methylation; r-loop; naive; pluripotency; formative; primed; tet1; dnmt3; zfp281
Journal Title:	Developmental Cell
Volume:	59
Issue:	4
ISSN:	1534-5807
Publisher:	Cell Press
Date Published:	2024-02-26
Start Page:	465
End Page:	481.e6
Language:	English
DOI:	10.1016/j.devcel.2023.12.018
PUBMED:	38237590
PROVIDER:	scopus
PMCID:	PMC10923053
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85182655515&doi=10.1016%2fj.devcel.2023.12.018&partnerID=40&md5=2bee83bdf5f5e90bb9fea0e8e91be295
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/214002