DNA methylation in the gene body influences MeCP2-mediated gene repression
Abstract
Mutations in the methyl-CpG binding protein 2 (MECP2) lead to the severe neurological disorder Rett syndrome, but our understanding of how MeCP2 regulates gene expression in the brain has been limited. Recently we uncovered evidence that MeCP2 controls transcription of very long genes with critical neuronal functions by binding a unique form of DNA methylation, enriched in neurons. Here, we provide evidence that MeCP2 represses transcription by binding within transcribed regions of genes. We show that this repressive effect is proportional to the total number of methylated DNA binding sites for MeCP2 within each gene. Our findings suggest a model in which MeCP2 represses transcription of long neuronal genes that contain many methylated binding sites by impeding transcriptional elongation.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- December 2016
- DOI:
- 10.1073/pnas.1618737114
- Bibcode:
- 2016PNAS..11315114K