In vivo binding of PRDM9 reveals interactions with noncanonical genomic sites

被引:50
作者
Grey, Corinne [1 ]
Clement, Julie A. J. [1 ]
Buard, Jerome [1 ]
Leblanc, Benjamin [2 ]
Gut, Ivo [3 ,4 ]
Gut, Marta [3 ,4 ]
Duret, Laurent [5 ]
de Massy, Bernard [1 ]
机构
[1] Univ Montpellier, CNRS, UMR9002, Inst Genet Humaine, F-34396 Montpellier 05, France
[2] Univ Copenhagen, BRIC, DK-2200 Copenhagen, Denmark
[3] BIST, CRG, CNAG CRG, Barcelona 08028, Spain
[4] UPF, Barcelona 08003, Spain
[5] Univ Claude Bernard, Univ Lyon, CNRS, Lab Biometrie & Biol Evolut,UMR 5558, F-69100 Villeurbanne, France
基金
欧洲研究理事会;
关键词
STRAND BREAK FORMATION; MEIOTIC RECOMBINATION INITIATION; REPAIR PATHWAY CHOICE; H3; LYSINE; 36; HOMOLOGOUS RECOMBINATION; CHROMOSOME SYNAPSIS; GENE CONVERSION; MOUSE GENOME; DNA; MICE;
D O I
10.1101/gr.217240.116
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In mouse and human meiosis, DNA double-strand breaks (DSBs) initiate homologous recombination and occur at specific sites called hotspots. The localization of these sites is determined by the sequence-specific DNA binding domain of the PRDM9 histone methyl transferase. Here, we performed an extensive analysis of PRDM9 binding in mouse spermatocytes. Unexpectedly, we identified a noncanonical recruitment of PRDM9 to sites that lack recombination activity and the PRDM9 binding consensus motif. These sites include gene promoters, where PRDM9 is recruited in a DSB-dependent manner. Another subset reveals DSB-independent interactions between PRDM9 and genomic sites, such as the binding sites for the insulator protein CTCF. We propose that these DSB-independent sites result from interactions between hotspot-bound PRDM9 and genomic sequences located on the chromosome axis.
引用
收藏
页码:580 / 590
页数:11
相关论文
共 71 条
[71]   Meiotic chromosomes: Integrating structure and function [J].
Zickler, D ;
Kleckner, N .
ANNUAL REVIEW OF GENETICS, 1999, 33 :603-754