HENMT1 and piRNA stability are required for adult male germ cell transposon repression and to define the spermatogenic program in the mouse
Files
(Published version)
Date
2015
Authors
Lim, S.
Qu, Z.
Kortschak, R.
Lawrence, D.
Geoghegan, J.
Hempfling, A.
Bergmann, M.
Goodnow, C.
Ormandy, C.
Wong, L.
Editors
Frye, M.
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
PLoS Genetics, 2015; 11(10):e1005620-1-e1005620-30
Statement of Responsibility
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
Conference Name
Abstract
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.
School/Discipline
Dissertation Note
Provenance
Description
Access Status
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