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...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-10-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC4619860?pdf=render |
| _version_ | 1830083411581075456 |
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| author | Shu 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 |
| author_facet | Shu 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 |
| author_sort | Shu Ly Lim |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T16:20:54Z |
| format | Article |
| id | doaj.art-696a274f282f4f478e57fd44243324b3 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-14T16:20:54Z |
| publishDate | 2015-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-696a274f282f4f478e57fd44243324b32022-12-21T22:54:48ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042015-10-011110e100562010.1371/journal.pgen.1005620HENMT1 and piRNA Stability Are Required for Adult Male Germ Cell Transposon Repression and to Define the Spermatogenic Program in the Mouse.Shu Ly LimZhi Peng QuR Daniel KortschakDavid M LawrenceJoel GeogheganAnna-Lena HempflingMartin BergmannChristopher C GoodnowChristopher J OrmandyLee WongJeff MannHamish S ScottDuangporn JamsaiDavid L AdelsonMoira K O'BryanpiRNAs 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.http://europepmc.org/articles/PMC4619860?pdf=render |
| spellingShingle | Shu 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 HENMT1 and piRNA Stability Are Required for Adult Male Germ Cell Transposon Repression and to Define the Spermatogenic Program in the Mouse. PLoS Genetics |
| title | 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_short | 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 |
| url | http://europepmc.org/articles/PMC4619860?pdf=render |
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