Neuronal cell depolarization induces intragenic chromatin modifications affecting NCAM alternative splicing.

ABSTRACT: In search for physiological pathways affecting alternative splicing through its kinetic coupling with transcription, we found that membrane depolarization of neuronal cells triggers the skipping of exon 18 from the neural cell adhesion molecule (NCAM) mRNA, independently of the calcium/calmodulin protein kinase IV pathway. We show that this exon responds to RNA polymerase II elongation, because its inclusion is increased by a slow polymerase II mutant. Depolarization affects the chromatin template in a specific way, by causing H3K9 hyper-acetylation restricted to an internal region of the NCAM gene surrounding the alternative exon. This intragenic histone hyper-acetylation is not paralleled by acetylation at the promoter, is associated with chromatin relaxation, and is linked to H3K36 tri-

SUBMITTER: Schor IE 

PROVIDER: S-EPMC2657401 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature