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.
Department of Medical Microbiology and Immunology, Rowe Program in Human Genetics, School of Medicine, University of California, 1 Shields Avenue, Davis, CA 95616, USA.
Dag H
DH
Yasui
Sailaja
S
Peddada
Mark C
MC
Bieda
Roxanne O
RO
Vallero
Amber
A
Hogart
Raman P
RP
Nagarajan
Karen N
KN
Thatcher
Peggy J
PJ
Farnham
Janine M
JM
Lasalle
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