Lsh is required for meiotic chromosome synapsis and retrotransposon silencing in female germ cells.
Lymphoid specific helicase (Lsh) is a major epigenetic regulator that is essential for DNA methylation and transcriptional silencing of parasitic elements in the mammalian genome. However, whether Lsh is involved in the regulation of chromatin-mediated processes during meiosis is not known. Here, we show that Lsh is essential for the completion of meiosis and transcriptional repression of repetitive elements in the female gonad. Oocytes from Lsh knockout mice exhibit demethylation of transposable elements and tandem repeats at pericentric heterochromatin, as well as incomplete chromosome synapsis associated with persistent RAD51 foci and gammaH2AX phosphorylation. Failure to load crossover-associated foci results in the generation of non-exchange chromosomes. The severe oocyte loss observed and lack of ovarian follicle formation, together with the patterns of Lsh nuclear compartmentalization in the germ line, demonstrate that Lsh has a critical and previously unidentified role in epigenetic gene silencing and maintenance of genomic stability during female meiosis.
De La Fuente
Rabindranath
R
Female Germ Cell Biology Group, Department of Clinical Studies, Center for Animal Transgenesis and Germ Cell Research, School of Veterinary Medicine, University of Pennsylvania, New Bolton Center, PA 19348, USA. rfuente@vet.upenn.edu
Baumann
Claudia
C
Fan
Tao
T
Schmidtmann
Anja
A
Dobrinski
Ina
I
Muegge
Kathrin
K
D000818:Animals; D023902:Chromosome Pairing; D033481:Chromosomes, Mammalian / Q000378:metabolism*; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D005260:Female; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006570:Heterochromatin / Q000378:metabolism; D008540:Meiosis; D051379:Mice; D009865:Oocytes / Q000166:cytology*; D010053:Ovary / Q000166:cytology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D018626:Retroelements / Q000235:genetics*; D014960:X Chromosome / Q000378:metabolism
D006570:Heterochromatin; D012333:RNA, Messenger; D018626:Retroelements; D004265:DNA Helicases; C491758:lymphoid specific helicase, mouse