HENMT1 and piRNA stability are required for adult male germ cell transposon repression and to define the spermatogenic program in the mouse

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dc.contributor.authorLim, S.
dc.contributor.authorQu, Z.
dc.contributor.authorKortschak, R.
dc.contributor.authorLawrence, D.
dc.contributor.authorGeoghegan, J.
dc.contributor.authorHempfling, A.
dc.contributor.authorBergmann, M.
dc.contributor.authorGoodnow, C.
dc.contributor.authorOrmandy, C.
dc.contributor.authorWong, L.
dc.contributor.authorMann, J.
dc.contributor.authorScott, H.
dc.contributor.authorJamsai, D.
dc.contributor.authorAdelson, D.
dc.contributor.authorO'Bryan, M.
dc.contributor.editorFrye, M.
dc.date.issued2015
dc.description.abstractpiRNAs are critical for transposable element (TE) repression and germ cell survival during the early phases of spermatogenesis, however, their role in adult germ cells and the relative importance of piRNA methylation is poorly defined in mammals. Using a mouse model of HEN methyltransferase 1 (HENMT1) loss-of-function, RNA-Seq and a range of RNA assays we show that HENMT1 is required for the 2' O-methylation of mammalian piRNAs. HENMT1 loss leads to piRNA instability, reduced piRNA bulk and length, and ultimately male sterility characterized by a germ cell arrest at the elongating germ cell phase of spermatogenesis. HENMT1 loss-of-function, and the concomitant loss of piRNAs, resulted in TE de-repression in adult meiotic and haploid germ cells, and the precocious, and selective, expression of many haploid-transcripts in meiotic cells. Precocious expression was associated with a more active chromatin state in meiotic cells, elevated levels of DNA damage and a catastrophic deregulation of the haploid germ cell gene expression. Collectively these results define a critical role for HENMT1 and piRNAs in the maintenance of TE repression in adult germ cells and setting the spermatogenic program.
dc.description.statementofresponsibilityShu Ly Lim, Zhi Peng Qu, R. Daniel Kortschak, David M. Lawrence, Joel Geoghegan, Anna-Lena Hempfling, Martin Bergmann, Christopher C. Goodnow, Christopher J. Ormandy, Lee Wong, Jeff Mann, Hamish S. Scott, Duangporn Jamsai, David L. Adelson, Moira K. O, Bryan
dc.identifier.citationPLoS Genetics, 2015; 11(10):e1005620-1-e1005620-30
dc.identifier.doi10.1371/journal.pgen.1005620
dc.identifier.issn1553-7404
dc.identifier.issn1553-7390
dc.identifier.orcidKortschak, R. [0000-0001-8295-2301]
dc.identifier.orcidLawrence, D. [0000-0001-5464-5830]
dc.identifier.orcidScott, H. [0000-0002-5813-631X]
dc.identifier.orcidAdelson, D. [0000-0003-2404-5636]
dc.identifier.orcidO'Bryan, M. [0000-0001-7298-4940]
dc.identifier.urihttp://hdl.handle.net/2440/97275
dc.language.isoen
dc.publisherPublic Library of Science
dc.relation.grantARC
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1058356
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/481310
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1023059
dc.rights© 2015 Lim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
dc.source.urihttps://doi.org/10.1371/journal.pgen.1005620
dc.subjectGerm Cells
dc.subjectChromatin
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectInfertility, Male
dc.subjectMethyltransferases
dc.subjectRNA, Small Interfering
dc.subjectDNA Transposable Elements
dc.subjectSpermatogenesis
dc.subjectGene Expression Regulation, Developmental
dc.subjectRNA Stability
dc.subjectMale
dc.subjectBasic Helix-Loop-Helix Transcription Factors
dc.titleHENMT1 and piRNA stability are required for adult male germ cell transposon repression and to define the spermatogenic program in the mouse
dc.typeJournal article
pubs.publication-statusPublished

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