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

TY - JOUR

T1 - X chromosome-wide analyses of genomic DNA methylation states and gene expression in male and female neutrophils

AU - Yasukochi, Yukio

AU - Maruyama, Osamu

AU - Mahajan, Milind C.

AU - Padden, Carolyn

AU - Euskirchen, Ghia M.

AU - Schulz, Vincent

AU - Hirakawa, Hideki

AU - Kuhara, Satoru

AU - Pan, Xing Hua

AU - Newburger, Peter E.

AU - Snyder, Michael

AU - Weissman, Sherman M.

PY - 2010/2/23

Y1 - 2010/2/23

N2 - 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.

AB - 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.

KW - DNA methylation

KW - High-throughput sequencing

KW - X inactivation

UR - https://www.scopus.com/pages/publications/77649263930

UR - https://www.scopus.com/pages/publications/77649263930#tab=citedBy

U2 - 10.1073/pnas.0914812107

DO - 10.1073/pnas.0914812107

M3 - Article

C2 - 20133578

SN - 0027-8424

VL - 107

SP - 3704

EP - 3709

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 8

ER -