Integrated epigenomic analyses of neuronal MeCP2 reveal a role for long-range interaction with active genes
Abstract
Mutations in MECP2 cause the autism-spectrum disorder Rett syndrome. MeCP2 is predicted to bind to methylated promoters and silence transcription. However, the first large-scale mapping of neuronal MeCP2-binding sites on 26.3 Mb of imprinted and nonimprinted loci revealed that 59% of MeCP2-binding sites are outside of genes and that only 6% are in CpG islands. Integrated genome-wide promoter analysis of MeCP2 binding, CpG methylation, and gene expression revealed that 63% of MeCP2-bound promoters are actively expressed and that only 6% are highly methylated. These results indicate that the primary function of MeCP2 is not the silencing of methylated promoters.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- December 2007
- DOI:
- 10.1073/pnas.0707442104
- Bibcode:
- 2007PNAS..10419416Y