RT Journal Article
SR Electronic
T1 Dynamic reorganization of nuclear architecture during human cardiogenesis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 222877
DO 10.1101/222877
A1 Paul A. Fields
A1 Vijay Ramani
A1 Giancarlo Bonora
A1 Gurkan Yardimci
A1 Alessandro Bertero
A1 Hans Reinecke
A1 Lil Pabon
A1 William S. Noble
A1 Jay Shendure
A1 Charles E. Murry
YR 2017
UL http://biorxiv.org/content/early/2017/11/21/222877.abstract
AB 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.