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Defective germline reprogramming rewires the spermatogonial transcriptome.

TitleDefective germline reprogramming rewires the spermatogonial transcriptome.
Publication TypeJournal Article
Year of Publication2018
AuthorsVasiliauskaite L, Berrens RV, Ivanova I, Carrieri C, Reik W, Enright AJ, O'Carroll D
JournalNat Struct Mol Biol
Volume25
Issue5
Pagination394-404
Date Published2018 May
ISSN1545-9985
Abstract

Defective germline reprogramming in Piwil4 (Miwi2)- and Dnmt3l-deficient mice results in the failure to reestablish transposon silencing, meiotic arrest and progressive loss of spermatogonia. Here we sought to understand the molecular basis for this spermatogonial dysfunction. Through a combination of imaging, conditional genetics and transcriptome analysis, we demonstrate that germ cell elimination in the respective mutants arises as a result of defective de novo genome methylation during reprogramming rather than because of a function for the respective factors within spermatogonia. In both Miwi2 and Dnmt3l spermatogonia, the intracisternal-A particle (IAP) family of endogenous retroviruses is derepressed, but, in contrast to meiotic cells, DNA damage is not observed. Instead, we find that unmethylated IAP promoters rewire the spermatogonial transcriptome by driving expression of neighboring genes. Finally, spermatogonial numbers, proliferation and differentiation are altered in Miwi2 and Dnmt3l mice. In summary, defective reprogramming deregulates the spermatogonial transcriptome and may underlie spermatogonial dysfunction.

DOI10.1038/s41594-018-0058-0
Alternate JournalNat. Struct. Mol. Biol.
PubMed ID29728652
PubMed Central IDPMC6086329
Publication institute
CRM