Dual histone methyl reader ZCWPW1 facilitates repair of meiotic double strand breaks in male mice

被引:25
|
作者
Mahgoub, Mohamed [1 ]
Paiano, Jacob [2 ,3 ]
Bruno, Melania [1 ]
Wu, Wei [2 ]
Pathuri, Sarath [4 ]
Zhang, Xing [4 ]
Ralls, Sherry [1 ]
Cheng, Xiaodong [4 ]
Nussenzweig, Andre [2 ]
Macfarlan, Todd S. [1 ]
机构
[1] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA
[2] NCI, Lab Genome Integr, NIH, Bethesda, MD 20892 USA
[3] Univ Penn, Immunol Grad Grp, Philadelphia, PA 19104 USA
[4] Univ Texas MD Anderson Canc Ctr, Dept Epigenet & Mol Carcinogenesis, Houston, TX 77030 USA
来源
ELIFE | 2020年 / 9卷
基金
美国国家卫生研究院;
关键词
SINGLE-NUCLEOTIDE POLYMORPHISMS; PRDM9 MEISETZ GENE; RECOMBINATION HOTSPOTS; METHYLTRANSFERASE ACTIVITY; CW DOMAIN; BINDING; ALIGNMENT; REVEALS; NUCLEOSOMES; CROSSOVERS;
D O I
10.7554/eLife.53360
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Meiotic crossovers result from homology-directed repair of DNA double-strand breaks (DSBs). Unlike yeast and plants, where DSBs are generated near gene promoters, in many vertebrates DSBs are enriched at hotspots determined by the DNA binding activity of the rapidly evolving zinc finger array of PRDM9 (PR domain zinc finger protein 9). PRDM9 subsequently catalyzes tri-methylation of lysine 4 and lysine 36 of Histone H3 in nearby nucleosomes. Here, we identify the dual histone methylation reader ZCWPW1, which is tightly co-expressed during spermatogenesis with Prdm9, as an essential meiotic recombination factor required for efficient repair of PRDM9-dependent DSBs and for pairing of homologous chromosomes in male mice. In sum, our results indicate that the evolution of a dual histone methylation writer/reader (PRDM9/ZCWPW1) system in vertebrates remodeled genetic recombination hotspot selection from an ancestral static pattern near genes towards a flexible pattern controlled by the rapidly evolving DNA binding activity of PRDM9.
引用
收藏
页数:25
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