X chromosome-wide analyses of genomic DNA methylation states and gene expression in male and female neutrophils.
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.
Department of Genetics, Yale University School of Medicine, New Haven, CT 06520-8064, USA.
Yukio
Y
Yasukochi
Osamu
O
Maruyama
Milind C
MC
Mahajan
Carolyn
C
Padden
Ghia M
GM
Euskirchen
Vincent
V
Schulz
Hideki
H
Hirakawa
Satoru
S
Kuhara
Xing-Hua
XH
Pan
Peter E
PE
Newburger
Michael
M
Snyder
Sherman M
SM
Weissman
D041321:Chromosomes, Human, X / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D050172:Genes, X-Linked; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012737:Sex Factors