Tet inactivation disrupts YY1 binding and long-range chromatin interactions during embryonic heart development. Nat Commun 2019 Sep 20;10(1):4297
Date
09/22/2019Pubmed ID
31541101Pubmed Central ID
PMC6754421DOI
10.1038/s41467-019-12325-zScopus ID
2-s2.0-85072523190 (requires institutional sign-in at Scopus site) 74 CitationsAbstract
Tet-mediated DNA demethylation plays an important role in shaping the epigenetic landscape and chromatin accessibility to control gene expression. While several studies demonstrated pivotal roles of Tet in regulating embryonic development, little is known about their functions in heart development. Here we analyze DNA methylation and hydroxymethylation dynamics during early cardiac development in both human and mice. We find that cardiac-specific deletion of Tet2 and Tet3 in mice (Tet2/3-DKO) leads to ventricular non-compaction cardiomyopathy (NCC) with embryonic lethality. Single-cell RNA-seq analyses reveal a reduction in cardiomyocyte numbers and transcriptional reprogramming in cardiac tissues upon Tet2/3 depletion. Impaired DNA demethylation and reduced chromatin accessibility in Tet2/3-DKO mice further compromised Ying-yang1 (YY1) binding to its genomic targets, and perturbed high-order chromatin organization at key genes involved in heart development. Our studies provide evidence of the physiological role of Tet in regulating DNA methylation dynamics and chromatin organization during early heart development.
Author List
Fang S, Li J, Xiao Y, Lee M, Guo L, Han W, Li T, Hill MC, Hong T, Mo W, Xu R, Zhang P, Wang F, Chang J, Zhou Y, Sun D, Martin JF, Huang YAuthor
Yang Xiao Assistant Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCardiomyopathies
Catalytic Domain
Cell Differentiation
Chromatin
DNA Demethylation
DNA Methylation
DNA-Binding Proteins
Dioxygenases
Embryonic Development
Gene Expression Profiling
Gene Expression Regulation, Developmental
Heart
Humans
Mice
Mice, Inbred C57BL
Mice, Knockout
Myocytes, Cardiac
Organogenesis
Proto-Oncogene Proteins
YY1 Transcription Factor
