replaced
January 5th, 2018 at 3:13am
Note: Replaced Biorxiv
Overview
Abstract
While chromosomal architecture varies among cell types, little is known about how this organization is established or its role in development. We integrated Hi-C, RNA-seq and ATAC-seq during cardiac differentiation from human pluripotent stem cells to generate a comprehensive profile of chromosomal architecture. We identified active and repressive domains that are dynamic during cardiogenesis and recapitulate in vivo cardiomyocytes. During differentiation, heterochromatic regions condense in cis . In contrast, many cardiac-specific genes, such as TTN (titin), decompact and transition to an active compartment coincident with upregulation. Moreover, we identify a network of genes, including TTN , that share the heart-specific splicing factor, RBM20, and become associated in trans during differentiation, suggesting the existence of a 3D nuclear splicing factory. Our results demonstrate both the dynamic nature in nuclear architecture and provide insights into how developmental genes are coordinately regulated. One Sentence Summary The three-dimensional structure of the human genome is dynamically regulated both globally and locally during cardiogenesis.
Authors
Paul A. Fields • Vijay Ramani • Giancarlo Bonora • Gurkan Yardimci • Alessandro Bertero • Hans Reinecke • Lil Pabon • William S. Noble • Jay Shendure • Charles E. Murry
Link
Journal
bioRxiv
doi:10.1101/222877
Published
November 21st, 2017