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Science 23 February 2007:
Vol. 315. no. 5815, pp. 1141 - 1143
DOI: 10.1126/science.1136352
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Reports

Gene Body-Specific Methylation on the Active X Chromosome

Asaf Hellman and Andrew Chess

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.

Center for Human Genetic Research and Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, MA 02114, USA.

E-mail: hellman{at}chgr.mgh.harvard.edu (A.H.); chess{at}chgr.mgh.harvard.edu (A.C.)

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