X chromosome-wide analyses of genomic DNA methylation states and gene expression in male and female neutrophils.
X chromosome-wide analyses of genomic DNA methylation states and gene expression in male and female neutrophils.
复制标题
对男性和女性中性粒细胞基因组 DNA 甲基化状态和基因表达进行 X 染色体全分析。
DOI：
10.1073/pnas.0914812107
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发表时间：
2010
影响因子：
11.1
通讯作者：
Weissman,ShermanM
中科院分区：
文献类型：
--
作者：
Yasukochi,Yukio;Maruyama,Osamu;Mahajan,MilindC;Padden,Carolyn;Euskirchen,GhiaM;Schulz,Vincent;Hirakawa,Hideki;Kuhara,Satoru;Pan,Xing-Hua;Newburger,PeterE;Snyder,Michael;Weissman,ShermanM
通过对 HpaII 和 MspI 消化片段进行高通量测序来鉴定男性和女性中性粒细胞 X 染色体的 DNA 甲基化状态。在 X 染色体上的基因间和基因内区域，CpG 岛外的位点在两性中都严重高甲基化，程度相同。在女性和男性中，近一半的 X 染色体启动子要么低甲基化，要么高甲基化。近三分之一的 X 染色体启动子在女性中是低甲基化和异质甲基化位点的混合物，而在男性中是低甲基化的。因此，大部分在失活 X 染色体上沉默的基因在其启动子区域被低甲基化。这些基因通常属于 X 染色体进化上较年轻的层。在两个以上位点低甲基化的启动子包含大部分在失活的 X 染色体上逃脱沉默的基因。无论失活 X 染色体的甲基化状态如何，女性和男性中 X 连锁基因的总体表达水平没有区别。因此，除了DNA甲基化之外，其他因素也参与了中性粒细胞基因剂量补偿的微调。
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.