Tet-mediated DNA methylation oxidation plays an important role in shaping the epigenetic landscapes and chromatin accessibility during gene expression. While several studies demonstrated pivotal roles of Tet proteins in regulating embryonic development, little is known about their functions in heart development. Here we systemetically analyzed DNA methylation and hydroxymethylation dynamics during early cardiac development in both human and mice. We discovered that cardiac-specific deletion of Tet2 and Tet3 in mice (Tet2/3-DKO) led to ventricular non-compaction cardiomyopathy (NCC) with embryonic lethality. Single-cell and bulk RNA-seq analyses revealed dramatic decrease of cardiomyocytes in Tet2/3-DKO heart tissues. Impaired DNA demethylation and chromatin accessibility in Tet2/3-DKO mice further compromised chromatin association of a key transcription factor, Ying-yang1 (YY1), and reduced long-range promoter-enhancer interactions at key genes involved in cardiac development. Taken together, our studies establish the physiological role of Tet proteins in the regulation of DNA methylation dynamics and chromatin configuration during embryonic heart development in mammals. SOURCE: Jia Li (jli@ibt.tamhsc.edu) - Deqiang Sun Texas A&M U Health Science Center

Pluto Bioinformatics

GSE121671: Tet inactivation disrupts YY1 binding and long-range chromatin interactions to cause developmental defects in embryonic heart