Calcium-mediated histone modifications regulate alternative splicing in cardiomyocytes.

ABSTRACT: In cardiomyocytes, calcium is known to control gene expression at the level of transcription, whereas its role in regulating alternative splicing has not been explored. Here we report that, in mouse primary or embryonic stem cell-derived cardiomyocytes, increased calcium levels induce robust and reversible skipping of several alternative exons from endogenously expressed genes. Interestingly, we demonstrate a calcium-mediated splicing regulatory mechanism that depends on changes of histone modifications. Specifically, the regulation occurs through changes in calcium-responsive kinase activities that lead to alterations in histone modifications and subsequent changes in the transcriptional elongation rate and exon skipping. We demonstrate that increased intracellular calcium levels lead to

SUBMITTER: Sharma A 

PROVIDER: S-EPMC4246288 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature