MORC1 represses transposable elements in the mouse male germline
Abstract
The Microrchidia (Morc) family of GHKL ATPases are present in a wide variety of prokaryotic and eukaryotic organisms but are of largely unknown function. Genetic screens in Arabidopsis thaliana have identified Morc genes as important repressors of transposons and other DNA-methylated and silent genes. MORC1-deficient mice were previously found to display male-specific germ cell loss and infertility. Here we show that MORC1 is responsible for transposon repression in the male germline in a pattern that is similar to that observed for germ cells deficient for the DNA methyltransferase homologue DNMT3L. Morc1 mutants show highly localized defects in the establishment of DNA methylation at specific classes of transposons, and this is associated with failed transposon silencing at these sites. Our results identify MORC1 as an important new regulator of the epigenetic landscape of male germ cells during the period of global de novo methylation.
Additional Information
© 2014 Macmillan Publishers Limited. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ Received 12 September 2014; Accepted 7 November 2014; Published 12 December 2014. We acknowledge the UCLA BSCRC Flow Cytometry core for flow and FACS assistance, and the UCLA BSCRC High Throughput Sequencing Core. Bryan Cullen provided anti-IAP Gag antibody and Alexander Bortvin provided anti-LINE ORF1p antibody. Jiamu Du and Dinshaw Patel provided recombinant MORC1 coiled-coil domain to raise antibody. W.A.P. is supported by the Jane Coffin Childs Memorial Fund for Medical Research. H.S. is an HHMI Fellow of the Damon Runyon Cancer Research Foundation (DRG-2194-14). W.L. is supported by a grant from the Chinese Scholar Council. This work was supported by grants from the NIH (R01 HD058047 and DP2 OD007371A), a Research Award from the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research and the Nogradi Fund, the Searle Scholar and the Packard Fellowship Awards, and an ANR grant ("TranspoFertil"). S.E.J. is an investigator of the Howard Hughes Medical Institute.Attached Files
Published - ncomms6795.pdf
Supplemental Material - ncomms6795-s1.pdf
Supplemental Material - ncomms6795-s2.xlsx
Supplemental Material - ncomms6795-s3.xlsx
Supplemental Material - ncomms6795-s4.xlsx
Supplemental Material - ncomms6795-s5.xlsx
Supplemental Material - ncomms6795-s6.xlsx
Erratum - ncomms8604.pdf
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Additional details
- PMCID
- PMC4268658
- Eprint ID
- 54464
- Resolver ID
- CaltechAUTHORS:20150205-164216193
- Jane Coffin Childs Memorial Fund for Medical Research
- Damon Runyon Cancer Research Foundation
- DRG-2194-14
- Chinese Scholar Council
- NIH
- R01 HD058047
- NIH
- DP2 OD007371A
- Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research
- Nogradi Fund
- Searle Scholars Program
- David and Lucile Packard Foundation
- Agence Nationale pour la Recherche (ANR)
- Created
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2015-02-06Created from EPrint's datestamp field
- Updated
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2023-06-01Created from EPrint's last_modified field