DOI: 10.1101/485961Dec 4, 2018Paper

3D Chromatin Architecture Remodeling during Human Cardiomyocyte Differentiation Reveals A Role Of HERV-H In Demarcating Chromatin Domains

BioRxiv : the Preprint Server for Biology
Yanxiao ZhangBing Ren

Abstract

Dynamic restructuring of chromatin architecture has been implicated in cell-type specific gene regulatory programs; yet, how chromatin remodels during lineage specification remains to be elucidated. Through interrogating chromatin reorganization during human cardiomyocyte differentiation, we uncover dynamic chromatin interactions between genes and distal regulatory elements harboring noncoding variants associated with adult and congenital heart diseases. Unexpectedly, we also discover a new class of human pluripotent stem cell (PSC)-specific topologically associating domains (TAD) that are created by the actively transcribed endogenous retrotransposon HERV-H. Deletion or silencing of specific HERV-H elements eliminates corresponding TAD boundaries, while de novo insertion of HERV-H can introduce new chromatin domain boundaries in human PSCs. Furthermore, comparative analysis of chromatin architecture in other species that lack HERV-H sequences supports a role for actively transcribed HERV-H in demarcating human PSC-specific TADs. The biological role of HERV-H is further underscored by the observation that deletion of a specific HERV-H reduces transcription of genes upstream and facilitates cell differentiation. Overall, our res...Continue Reading

Related Concepts

Cell Differentiation Process
Chromatin
Gene Deletion
Genes
Genes, Regulator
Genome
Heart Diseases
Transcription, Genetic
Myocytes, Cardiac
Hypoxia

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