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HENMT1 and piRNA Stability Are Required for Adult Male Germ Cell Transposon Repression and to Define the Spermatogenic Program in the Mouse


Piwi-interacting RNAs (piRNAs) are small non-coding RNAs found in great abundance within both embryonic and adult male germ cells. Within embryonic germ cells, piRNAs have a well-recognized role in transposable element (TE) silencing, however, their role in adult cells remains poorly defined. Here we demonstrate that HENMT1 dysfunction and the resultant piRNA instability dramatically impacts multiple aspects of adult germ cell biology. Specifically, pachytene piRNAs are required to maintain TE silencing in adult germ cells and to set the spermatogenic gene expression program. piRNA loss leads to a more active chromatin state in the regulatory regions of numerous normally haploid germ cell genes and their precocious expression during meiosis, followed by a catastrophic deregulation of gene expression in haploid cells and male sterility.


Vyšlo v časopise: HENMT1 and piRNA Stability Are Required for Adult Male Germ Cell Transposon Repression and to Define the Spermatogenic Program in the Mouse. PLoS Genet 11(10): e32767. doi:10.1371/journal.pgen.1005620
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005620

Souhrn

Piwi-interacting RNAs (piRNAs) are small non-coding RNAs found in great abundance within both embryonic and adult male germ cells. Within embryonic germ cells, piRNAs have a well-recognized role in transposable element (TE) silencing, however, their role in adult cells remains poorly defined. Here we demonstrate that HENMT1 dysfunction and the resultant piRNA instability dramatically impacts multiple aspects of adult germ cell biology. Specifically, pachytene piRNAs are required to maintain TE silencing in adult germ cells and to set the spermatogenic gene expression program. piRNA loss leads to a more active chromatin state in the regulatory regions of numerous normally haploid germ cell genes and their precocious expression during meiosis, followed by a catastrophic deregulation of gene expression in haploid cells and male sterility.


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