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CXXC finger protein 1-mediated histone H3 lysine-4 trimethylation is essential for proper meiotic crossover formation in mice
Ist Teil von
Development (Cambridge), 2020-03, Vol.147 (6)
Ort / Verlag
England
Erscheinungsjahr
2020
Quelle
MEDLINE
Beschreibungen/Notizen
The most significant feature of meiosis is the recombination process during prophase I. CXXC finger protein 1 (CXXC1) binds to CpG islands and mediates the deposition of H3K4me3 by the SETD1 complex. CXXC1 is also predicted to recruit H3K4me3-marked regions to the chromosome axis for the generation of double-strand breaks (DSBs) in the prophase of meiosis. Therefore, we deleted
before the onset of meiosis with
The conditional knockout mice were completely sterile with spermatogenesis arrested at MII. Knockout of
led to a decrease in the H3K4me3 level from the pachytene to the MII stage and caused transcriptional disorder. Many spermatogenesis pathway genes were expressed early leading to abnormal acrosome formation in arrested MII cells. In meiotic prophase, deletion of
caused delayed DSB repair and improper crossover formation in cells at the pachytene stage, and more than half of the diplotene cells exhibited precocious homologous chromosome segregation in both male and female meiosis.
deletion also led to a significant decrease of H3K4me3 enrichment at DMC1-binding sites, which might compromise DSB generation. Taken together, our results show that CXXC1 is essential for proper meiotic crossover formation in mice and suggest that CXXC1-mediated H3K4me3 plays an essential role in meiotic prophase of spermatogenesis and oogenesis.