Department of Pediatrics
Medical Subject Headings
Chromosomes, Human, X; *DNA Methylation; Female; *Gene Expression; *Gene Expression Regulation; *Genes, X-Linked; Humans; Male; Neutrophils; Promoter Regions, Genetic; Sex Factors
Hematology | Oncology | Pediatrics
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.
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Citation: Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3704-9. Epub 2010 Feb 2. Link to article on publisher's website
Yasukochi, Yukio; Maruyama, Osamu; Mahajan, Milind C.; Padden, Carolyn; Euskirchen, Ghia M.; Schulz, Vincent; Hirakawa, Hideki; Kuhara, Satoru; Pan, Xing-Hua; Newburger, Peter E.; Snyder, Michael; and Weissman, Sherman M., "X chromosome-wide analyses of genomic DNA methylation states and gene expression in male and female neutrophils" (2010). Hematology/Oncology. 128.