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X chromosome-wide analyses of genomic DNA methylation states and gene expression in male and female neutrophils

By Yukio Yasukochi, Osamu Maruyama, Milind C. Mahajan, Carolyn Padden, Ghia M. Euskirchen, Vincent Schulz, Hideki Hirakawa, Satoru Kuhara, Xing-Hua Pan, Peter E. Newburger, Michael Snyder and Sherman M. Weissman

Abstract

The DNA methylation status of human X chromosomes from male and female neutrophils was identified by high-throughput sequencing of HpaII and MspI digested fragments. In the intergenic and intragenic regions on the X chromosome, the sites outside CpG islands were heavily hypermethylated to the same degree in both genders. Nearly half of X chromosome promoters were either hypomethylated or hypermethylated in both females and males. Nearly one third of X chromosome promoters were a mixture of hypomethylated and heterogeneously methylated sites in females and were hypomethylated in males. Thus, a large fraction of genes that are silenced on the inactive X chromosome are hypomethylated in their promoter regions. These genes frequently belong to the evolutionarily younger strata of the X chromosome. The promoters that were hypomethylated at more than two sites contained most of the genes that escaped silencing on the inactive X chromosome. The overall levels of expression of X-linked genes were indistinguishable in females and males, regardless of the methylation state of the inactive X chromosome. Thus, in addition to DNA methylation, other factors are involved in the fine tuning of gene dosage compensation in neutrophils

Topics: Biological Sciences
Publisher: National Academy of Sciences
OAI identifier: oai:pubmedcentral.nih.gov:2840519
Provided by: PubMed Central
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