@article{4c7126f1995247c2bd1e858efb497dbf,
title = "Tet inactivation disrupts YY1 binding and long-range chromatin interactions during embryonic heart development",
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.",
author = "Shaohai Fang and Jia Li and Yang Xiao and Minjung Lee and Lei Guo and Wei Han and Tingting Li and Hill, {Matthew C.} and Tingting Hong and William Mo and Rang Xu and Ping Zhang and Fen Wang and Jiang Chang and Yubin Zhou and Deqiang Sun and Martin, {James F.} and Yun Huang",
note = "Funding Information: We are grateful for Dr. Jianjun Shen and the MD Anderson Cancer Center next-generation sequencing core at Smithville (CPRIT RP120348 and RP170002), and the Epigenetic core in Institute of Biosciences and Technology at the Texas A&M University. This work was supported by grants from Cancer Prevention and Research Institute of Texas (RR140053 to Y.H., RP170660 to Y.Z., RP180131 to D.S.), the Innovation Award from American Heart Association (16IRG27250155 to Y.H.), the John S. Dunn Foundation Collaborative Research Award (to Y.H.), National Institute of Health grants (R01HL134780 to Y.H., R01HL146852 to Y.H., R01DE023177 to J.F.M., R01HL127717 to J.F.M., R01HL130804 to J.F.M., R01HL118761 to J.F.M., F31HL136065 to M.C.H., R01GM112003 to Y.Z., R01HL123953 to J.C.), the Welch Foundation (BE-1913-20190330 to Y.Z.), the American Cancer Society (RSG-18-043-01-LIB to YH; RSG-16-215-01-TBE to Y.Z.), Vivian L. Smith Foundation and MacDonald Research Fund Award (16RDM001 to J.F.M.), Transatlantic Network of Excellence Award LeDucq Foundation Transatlantic Networks of Excellence in Cardiovascular Research 14CVD01: “Defining genomic topology of atrial fibrillation.” (J.F.M.), and by an allocation from the Texas A&M University start-up funds (Y.H. and D.S.). Publisher Copyright: {\textcopyright} 2019, The Author(s).",
year = "2019",
month = dec,
day = "1",
doi = "10.1038/s41467-019-12325-z",
language = "English (US)",
volume = "10",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}