Scholarlink

Background <p>Several lines of evidence suggest that the sex-chromosome complement influences autosomal gene regulation and DNA methylation, however, the exact molecular mechanisms responsible for such effects remain elusive. X-linked epigenetic modifiers that escape X-chromosome inactivation, and hence have higher dosage in female cells, are the primary gene candidates for mediating the effects of X-dosage, whereas Y-linked paralogs may rescue such imbalance or have distinct effects on methylation.</p> Methods <p>Here, we tested the impacts of mutations in mouse histone lysine 4 demethylases <i>Kdm5c</i> (X-linked) and <i>Kdm5d</i> (Y-linked) on DNA methylation in mouse liver. KDM5C and KDM5D demethylate H3K4me2/3 thereby facilitating DNA methylation of their target DNA regions. Therefore, loss of either <i>Kdm5c</i> or <i>Kdm5d</i> is expected to reduce DNA methylation at such regions. We hypothesized that <i>Kdm5c</i> gene dosage was responsible for the X-dosage dependent DNA methylation in mouse liver and compared DNA methylation patterns in heterozygous mutant <i>Kdm5c+/-</i> and wild type females using whole genome bisulfite sequencing (WGBS) and DSS.</p> Results <p>We examined the impacts of mutations in <i>Kdm5c</i> or <i>Kdm5d</i> on genome-wide DNA methylation and found that they had different targets but tended to map close to H3K4me1-enriched regions. We also compared the <i>Kdm5c</i> and <i>Kdm5d</i> sensitive regions to regions with sex-chromosome complement dependent DNA methylation and found no overlaps.</p> Conclusions <p>In summary, while <i>Kdm5c</i> and <i>Kdm5d</i> have multi-locus effects on DNA methylation in mouse liver, they are unlikely to be solely responsible for sex-chromosome complement effects on DNA methylation in adult mouse liver.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

KDM5C and KDM5D influence DNA methylation in adult mouse liver

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月12日

查看全文
  • Emily Gibbons,
  • Kathleen Oros Klein,
  • Shinya Inoue,
  • Tohru Kimura,
  • Celia M. T. Greenwood,
  • Anna K. Naumova

摘要

Background

Several lines of evidence suggest that the sex-chromosome complement influences autosomal gene regulation and DNA methylation, however, the exact molecular mechanisms responsible for such effects remain elusive. X-linked epigenetic modifiers that escape X-chromosome inactivation, and hence have higher dosage in female cells, are the primary gene candidates for mediating the effects of X-dosage, whereas Y-linked paralogs may rescue such imbalance or have distinct effects on methylation.

Methods

Here, we tested the impacts of mutations in mouse histone lysine 4 demethylases Kdm5c (X-linked) and Kdm5d (Y-linked) on DNA methylation in mouse liver. KDM5C and KDM5D demethylate H3K4me2/3 thereby facilitating DNA methylation of their target DNA regions. Therefore, loss of either Kdm5c or Kdm5d is expected to reduce DNA methylation at such regions. We hypothesized that Kdm5c gene dosage was responsible for the X-dosage dependent DNA methylation in mouse liver and compared DNA methylation patterns in heterozygous mutant Kdm5c+/- and wild type females using whole genome bisulfite sequencing (WGBS) and DSS.

Results

We examined the impacts of mutations in Kdm5c or Kdm5d on genome-wide DNA methylation and found that they had different targets but tended to map close to H3K4me1-enriched regions. We also compared the Kdm5c and Kdm5d sensitive regions to regions with sex-chromosome complement dependent DNA methylation and found no overlaps.

Conclusions

In summary, while Kdm5c and Kdm5d have multi-locus effects on DNA methylation in mouse liver, they are unlikely to be solely responsible for sex-chromosome complement effects on DNA methylation in adult mouse liver.