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

作者: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; Weissman Sherman M*
来源:Proceedings of the National Academy of Sciences of the United States of America, 2010, 107(8): 3704-3709.
DOI:10.1073/pnas.0914812107

摘要

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.

  • 出版日期2010-2-23