Integrated epigenomic analyses of neuronal MeCP2 reveal a role for long-range interaction with active genes

DH Yasui, S Peddada, MC Bieda… - Proceedings of the …, 2007 - National Acad Sciences
DH Yasui, S Peddada, MC Bieda, RO Vallero, A Hogart, RP Nagarajan, KN Thatcher…
Proceedings of the National Academy of Sciences, 2007National Acad Sciences
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 …
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.
National Acad Sciences