MeCP2 Represses the Rate of Transcriptional Initiation of Highly Methylated Long Genes.

ABSTRACT: Mutations in the methyl-DNA-binding repressor protein MeCP2 cause the devastating neurodevelopmental disorder Rett syndrome. It has been challenging to understand how MeCP2 regulates transcription because MeCP2 binds broadly across the genome and MeCP2 mutations are associated with widespread small-magnitude changes in neuronal gene expression. We demonstrate here that MeCP2 represses nascent RNA transcription of highly methylated long genes in the brain through its interaction with the NCoR co-repressor complex. By measuring the rates of transcriptional initiation and elongation directly in the brain, we find that MeCP2 has no measurable effect on transcriptional elongation, but instead represses the rate at which Pol II initiates transcription of highly methylated long genes. These findi

SUBMITTER: Boxer LD 

PROVIDER: S-EPMC6982532 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature