| Literature DB >> 31541101 |
Shaohai Fang1, Jia Li1, Yang Xiao2,3, Minjung Lee1, Lei Guo1, Wei Han1, Tingting Li1, Matthew C Hill4, Tingting Hong1, William Mo1, Rang Xu5, Ping Zhang5, Fen Wang6, Jiang Chang6, Yubin Zhou6,7, Deqiang Sun8, James F Martin9,10,11,12, Yun Huang13,14,15.
Abstract
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.Entities:
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Year: 2019 PMID： 31541101 PMCID： PMC6754421 DOI： 10.1038/s41467-019-12325-z
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919