Gene body-specific methylation on the active X chromosome.
Differential DNA methylation is important for the epigenetic regulation of gene expression. Allele-specific methylation of the inactive X chromosome has been demonstrated at promoter CpG islands, but the overall pattern of methylation on the active X(Xa) and inactive X (Xi) chromosomes is unknown. We performed allele-specific analysis of more than 1000 informative loci along the human X chromosome. The Xa displays more than two times as much allele-specific methylation as Xi. This methylation is concentrated at gene bodies, affecting multiple neighboring CpGs. Before X inactivation, all of these Xa gene body-methylated sites are biallelically methylated. Thus, a bipartite methylation-demethylation program results in Xa-specific hypomethylation at gene promoters and hypermethylation at gene bodies. These results suggest a relationship between global methylation and expression potentiality.
Hellman
Asaf
A
Center for Human Genetic Research and Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, MA 02114, USA. hellman@chgr.mgh.harvard.edu
Chess
Andrew
A
D000483:Alleles; D002460:Cell Line; D041321:Chromosomes, Human, X / Q000235:genetics* / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D053595:Embryonic Stem Cells; D044127:Epigenesis, Genetic; D005260:Female; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006579:Heterozygote; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D049951:X Chromosome Inactivation