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

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

piRNAs 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 (HENMT...

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Main Authors: Lim, Shu Ly, Qu, Zhi Peng, Kortschak, R. Daniel, Lawrence, David M., Geoghegan, Joel, Hempfling, Anna-Lena, Bergmann, Martin, Goodnow, Christopher C., Ormandy, Christopher J., Wong, Lee, Mann, Jeff, Scott, Hamish S., Jamsai, Duangporn, Adelson, David L., O’Bryan, Moira K.
Format: Online
Language:English
Published: Public Library of Science 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4619860/
id pubmed-4619860
recordtype oai_dc
spelling pubmed-46198602015-10-29 HENMT1 and piRNA Stability Are Required for Adult Male Germ Cell Transposon Repression and to Define the Spermatogenic Program in the Mouse Lim, Shu Ly Qu, Zhi Peng Kortschak, R. Daniel Lawrence, David M. Geoghegan, Joel Hempfling, Anna-Lena Bergmann, Martin Goodnow, Christopher C. Ormandy, Christopher J. Wong, Lee Mann, Jeff Scott, Hamish S. Jamsai, Duangporn Adelson, David L. O’Bryan, Moira K. Research Article piRNAs 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. Public Library of Science 2015-10-23 /pmc/articles/PMC4619860/ /pubmed/26496356 http://dx.doi.org/10.1371/journal.pgen.1005620 Text en © 2015 Lim et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Lim, Shu Ly
Qu, Zhi Peng
Kortschak, R. Daniel
Lawrence, David M.
Geoghegan, Joel
Hempfling, Anna-Lena
Bergmann, Martin
Goodnow, Christopher C.
Ormandy, Christopher J.
Wong, Lee
Mann, Jeff
Scott, Hamish S.
Jamsai, Duangporn
Adelson, David L.
O’Bryan, Moira K.
spellingShingle Lim, Shu Ly
Qu, Zhi Peng
Kortschak, R. Daniel
Lawrence, David M.
Geoghegan, Joel
Hempfling, Anna-Lena
Bergmann, Martin
Goodnow, Christopher C.
Ormandy, Christopher J.
Wong, Lee
Mann, Jeff
Scott, Hamish S.
Jamsai, Duangporn
Adelson, David L.
O’Bryan, Moira K.
HENMT1 and piRNA Stability Are Required for Adult Male Germ Cell Transposon Repression and to Define the Spermatogenic Program in the Mouse
author_facet Lim, Shu Ly
Qu, Zhi Peng
Kortschak, R. Daniel
Lawrence, David M.
Geoghegan, Joel
Hempfling, Anna-Lena
Bergmann, Martin
Goodnow, Christopher C.
Ormandy, Christopher J.
Wong, Lee
Mann, Jeff
Scott, Hamish S.
Jamsai, Duangporn
Adelson, David L.
O’Bryan, Moira K.
author_sort Lim, Shu Ly
title HENMT1 and piRNA Stability Are Required for Adult Male Germ Cell Transposon Repression and to Define the Spermatogenic Program in the Mouse
title_short HENMT1 and piRNA Stability Are Required for Adult Male Germ Cell Transposon Repression and to Define the Spermatogenic Program in the Mouse
title_full HENMT1 and piRNA Stability Are Required for Adult Male Germ Cell Transposon Repression and to Define the Spermatogenic Program in the Mouse
title_fullStr HENMT1 and piRNA Stability Are Required for Adult Male Germ Cell Transposon Repression and to Define the Spermatogenic Program in the Mouse
title_full_unstemmed HENMT1 and piRNA Stability Are Required for Adult Male Germ Cell Transposon Repression and to Define the Spermatogenic Program in the Mouse
title_sort henmt1 and pirna stability are required for adult male germ cell transposon repression and to define the spermatogenic program in the mouse
description piRNAs 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.
publisher Public Library of Science
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4619860/
_version_ 1613492806249086976

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