Integrated epigenomic analyses of neuronal MeCP2 reveal a role for long-range interaction with active genes.
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.
Yasui
Dag H
DH
Department of Medical Microbiology and Immunology, Rowe Program in Human Genetics, School of Medicine, University of California, 1 Shields Avenue, Davis, CA 95616, USA.
Peddada
Sailaja
S
Bieda
Mark C
MC
Vallero
Roxanne O
RO
Hogart
Amber
A
Nagarajan
Raman P
RP
Thatcher
Karen N
KN
Farnham
Peggy J
PJ
Lasalle
Janine M
JM
D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D018899:CpG Islands; D019175:DNA Methylation; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D011401:Promoter Regions, Genetic; D015518:Rett Syndrome / Q000235:genetics*
D051783:Methyl-CpG-Binding Protein 2