Stage-specific regulation of DNA methylation by TET enzymes during human cardiac differentiation Journal Article

   

Authors:	Lan, Y.; Banks, K. M.; Pan, H.; Verma, N.; Dixon, G. R.; Zhou, T.; Ding, B.; Elemento, O.; Chen, S.; Huangfu, D.; Evans, T.
Article Title:	Stage-specific regulation of DNA methylation by TET enzymes during human cardiac differentiation
Abstract:	Changes in DNA methylation are associated with normal cardiogenesis, whereas altered methylation patterns can occur in congenital heart disease. Ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine (5mC) and promote locus-specific DNA demethylation. Here, we characterize stage-specific methylation dynamics and the function of TETs during human cardiomyocyte differentiation. Human embryonic stem cells (hESCs) in which all three TET genes are inactivated fail to generate cardiomyocytes (CMs), with altered mesoderm patterning and defective cardiac progenitor specification. Genome-wide methylation analysis shows TET knockout causes promoter hypermethylation of genes encoding WNT inhibitors, leading to hyperactivated WNT signaling and defects in cardiac mesoderm patterning. TET activity is also needed to maintain hypomethylated status and expression of NKX2-5 for subsequent cardiac progenitor specification. Finally, loss of TETs causes a set of cardiac structural genes to fail to be demethylated at the cardiac progenitor stage. Our data demonstrate key roles for TET proteins in controlling methylation dynamics at sequential steps during human cardiac development. © 2021 The Author(s)
Keywords:	cardiogenesis; wnt; epigenomics; hescs; nkx2-5; tmem88
Journal Title:	Cell Reports
Volume:	37
Issue:	10
ISSN:	2211-1247
Publisher:	Cell Press
Date Published:	2021-12-07
Start Page:	110095
Language:	English
DOI:	10.1016/j.celrep.2021.110095
PROVIDER:	scopus
PUBMED:	34879277
PMCID:	PMC11229417
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85120814063&doi=10.1016%2fj.celrep.2021.110095&partnerID=40&md5=5523b8a195e366bdcf2b777fa0aa26b9
Notes:	Article -- Export Date: 3 January 2022 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/191504