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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Alessandro Bertero, Paul A Fields, Vijay Ramani, Giancarlo Bonora, Galip G Yardimci, Hans Reinecke, Lil Pabon, William S Noble, Jay Shendure, Charles E Murry

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 RBM20 foci that drive spatial proximity between the TTN locus and other inter-chromosomal RBM20 targets such as CACNA1C and CAMK2D. This mechanism promotes RBM20-dependent alternative splicing of the resulting transcripts, indicating the existence of a cardiac-specific trans-interacting chromatin domain (TID) functioning as a splicing factory. More... »

PAGES

1538

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-019-09483-5

    DOI

    http://dx.doi.org/10.1038/s41467-019-09483-5

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1113184965

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30948719


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