G9a co-suppresses LINE1 elements in spermatogonia

Epigenetics & Chromatin

Dónal O’Carroll²  Srinath C Sampath¹  Srihari C Sampath¹  Stefano Comazzetto²  Monica Di Giacomo² 

[1] Genetics Department, Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA;European Molecular Biology Laboratory (EMBL), Mouse Biology Unit, Via Ramarini 32, Monterotondo Scalo 00015, Italy

关键词: piRNA and DNA methylation;    H3K9me2;    G9a;    IAP;    Retrotransposons;    LINE1;   

Others  :  1120532
DOI  :  10.1186/1756-8935-7-24

 received in 2014-05-27, accepted in 2014-08-26,  发布年份 2014

【 摘 要 】

Background

Repression of retrotransposons is essential for genome integrity and the development of germ cells. Among retrotransposons, the establishment of CpG DNA methylation and epigenetic silencing of LINE1 (L1) elements and the intracisternal A particle (IAP) endogenous retrovirus (ERV) is dependent upon the piRNA pathway during embryonic germ cell reprogramming. Furthermore, the Piwi protein Mili, guided by piRNAs, cleaves expressed L1 transcripts to post-transcriptionally enforce L1 silencing in meiotic cells. The loss of both DNA methylation and the Mili piRNA pathway does not affect L1 silencing in the mitotic spermatogonia where histone H3 lysine 9 dimethylation (H3K9me2) is postulated to co-repress these elements.

Results

Here we show that the histone H3 lysine 9 dimethyltransferase G9a co-suppresses L1 elements in spermatogonia. In the absence of both a functional piRNA pathway and L1 DNA methylation, G9a is both essential and sufficient to silence L1 elements. In contrast, H3K9me2 alone is insufficient to maintain IAP silencing in spermatogonia. The loss of all three repressive mechanisms has a major impact on spermatogonial populations inclusive of spermatogonial stem cells, with the loss of all germ cells observed in a high portion of seminiferous tubules.

Conclusions

Our study identifies G9a-mediated H3K9me2 as a novel and important L1 repressive mechanism in the germ line. We also demonstrate fundamental differences in the requirements for the maintenance of L1 and IAP silencing during adult spermatogenesis, where H3K9me2 is sufficient to maintain L1 but not IAP silencing. Finally, we demonstrate that repression of retrotransposon activation in spermatogonia is important for the survival of this population and testicular homeostasis.

【 授权许可】

   
2014 Di Giacomo et al.; licensee BioMed Central Ltd.

【 图 表 】

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