Dynamics of genome reorganization during human cardiogenesis reveal an RBM20-dependent splicing factory.

ABSTRACT: Functional changes in spatial genome organization during human development are poorly understood. Here we report a comprehensive profile of nuclear dynamics during human cardiogenesis from pluripotent stem cells by integrating Hi-C, RNA-seq and ATAC-seq. While chromatin accessibility and gene expression show complex on/off dynamics, large-scale genome architecture changes are mostly unidirectional. Many large cardiac genes transition from a repressive to an active compartment during differentiation, coincident with upregulation. We identify a network of such gene loci that increase their association inter-chromosomally, and are targets of the muscle-specific splicing factor RBM20. Genome editing studies show that TTN pre-mRNA, the main RBM20-regulated transcript in the heart, nucleates RBM

SUBMITTER: Bertero A 

PROVIDER: S-EPMC6449405 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature