The Dnmt3L ADD Domain Controls Cytosine Methylation Establishment during Spermatogenesis.
The Dnmt3L ADD Domain Controls Cytosine Methylation Establishment during Spermatogenesis.
复制标题
DNMT3L添加结构域控制精子发生过程中的胞嘧啶甲基化建立。
DOI：
10.1016/j.celrep.2015.01.021
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发表时间：
2015-02-17
期刊：
影响因子：
8.8
通讯作者：
Ooi SKT
中科院分区：
文献类型：
--
作者：
Vlachogiannis G;Niederhuth CE;Tuna S;Stathopoulou A;Viiri K;de Rooij DG;Jenner RG;Schmitz RJ;Ooi SKT
A critical aspect of mammalian gametogenesis is the reprogramming of genomic DNA methylation. The catalytically inactive adaptor Dnmt3L is essential to ensuring this occurs correctly, but the mechanism by which it functions is unclear. Using gene targeting to engineer a single-amino-acid mutation, we show that the Dnmt3L histone H3 binding domain (ADD) is necessary for spermatogenesis. Genome-wide single-base-resolution DNA methylome analysis of mutant germ cells revealed overall reductions in CG methylation at repetitive sequences and non-promoter CpG islands. Strikingly, we also observe an even more severe loss of non-CG methylation, suggesting an unexpected role for the ADD in this process. These epigenetic deficiencies were coupled with defects in spermatogonia, with mutant cells displaying marked changes in gene expression and reactivation of retrotransposons. Our results demonstrate that the Dnmt3L ADD is necessary for Dnmt3L function and full reproductive fitness. Full establishment of CG methylation during male gametogenesis requires Dnmt3L ADD Non-CG methylation establishment critically requires Dnmt3L ADD Correct spermatogenesis and fertility requires Dnmt3L ADD Defects are a consequence of altered gene expression and retroelements expression The adaptor protein Dnmt3L plays a crucial role in establishing cytosine methylation during male gametogenesis, but its mechanism of action is unclear. Vlachogiannis et al. now show that the N-terminal ADD domain is necessary for full methylation establishment, with CH sites being critically dependent on this domain.
