Genetic variation in the Y chromosome and sex-biased DNA methylation in somatic cells in the mouse.
Genetic variation in the Y chromosome and sex-biased DNA methylation in somatic cells in the mouse.
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DOI：
10.1007/s00335-022-09970-z
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发表时间：
2023-03
期刊：
影响因子：
2.5
通讯作者：
Naumova, Anna K.
中科院分区：
文献类型：
--
作者：
Batdorj, Enkhjin;AlOgayil, Najla;Zhuang, Qinwei Kim-Wee;Galvez, Jose Hector;Bauermeister, Klara;Nagata, Kei;Kimura, Tohru;Ward, Monika A.;Taketo, Teruko;Bourque, Guillaume;Naumova, Anna K.
几条证据表明，Y染色体的存在影响常染色体基因座的DNA甲基化。为了更好地了解Y染色体对常染色体DNA甲基化模式的影响及其对甲基化性别偏倚的贡献，我们使用来自具有不同性染色体补体和性腺性别组合的小鼠肝脏的全基因组亚硫酸氢盐测序甲基化数据来鉴定Y染色体依赖性差异甲基化区域（yDMR）。近90%的常染色体yDMR定位到转座因子（TE），其中大多数在XY小鼠中的甲基化程度低于XX或XO小鼠。对4个报告基因常染色体yDMR的随访分析显示，Y依赖性甲基化水平在大多数体细胞组织中是一致的，但在Y染色体来源不同的菌株中有所不同，这表明Y染色体的遗传变异影响常染色体区域的甲基化水平。与野生型小鼠相比，缺乏Y染色体q臂的小鼠（B6.NPYq-2）以及Kdm 5d功能丧失突变的小鼠的甲基化水平没有差异。因此，Y连锁的TE甲基化修饰基因可能位于Y染色体的短臂上，需要进一步的研究来鉴定该基因。在线版本包含补充材料，可通过10.1007/s 00335 -022-09970-z获得。
Several lines of evidence suggest that the presence of the Y chromosome influences DNA methylation of autosomal loci. To better understand the impact of the Y chromosome on autosomal DNA methylation patterns and its contribution to sex bias in methylation, we identified Y chromosome dependent differentially methylated regions (yDMRs) using whole-genome bisulfite sequencing methylation data from livers of mice with different combinations of sex-chromosome complement and gonadal sex. Nearly 90% of the autosomal yDMRs mapped to transposable elements (TEs) and most of them had lower methylation in XY compared to XX or XO mice. Follow-up analyses of four reporter autosomal yDMRs showed that Y-dependent methylation levels were consistent across most somatic tissues but varied in strains with different origins of the Y chromosome, suggesting that genetic variation in the Y chromosome influenced methylation levels of autosomal regions. Mice lacking the q-arm of the Y chromosome (B6.NPYq-2) as well as mice with a loss-of-function mutation in Kdm5d showed no differences in methylation levels compared to wild type mice. In conclusion, the Y-linked modifier of TE methylation is likely to reside on the short arm of Y chromosome and further studies are required to identify this gene. The online version contains supplementary material available at 10.1007/s00335-022-09970-z.
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