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Publication : Lsh is required for meiotic chromosome synapsis and retrotransposon silencing in female germ cells.

First Author  De La Fuente R Year  2006
Journal  Nat Cell Biol Volume  8
Issue  12 Pages  1448-54
PubMed ID  17115026 Mgi Jnum  J:140233
Mgi Id  MGI:3812299 Doi  10.1038/ncb1513
Citation  De La Fuente R, et al. (2006) Lsh is required for meiotic chromosome synapsis and retrotransposon silencing in female germ cells. Nat Cell Biol 8(12):1448-54
abstractText  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.
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