Functional Roles of Acetylated Histone Marks at Mouse Meiotic Recombination Hot Spots.
Meiotic recombination initiates following the formation of DNA double-strand breaks (DSBs) by the Spo11 endonuclease early in prophase I, at discrete regions in the genome coined "hot spots." In mammals, meiotic DSB site selection is directed in part by sequence-specific binding of PRDM9, a polymorphic histone H3 (H3K4Me3) methyltransferase. However, other chromatin features needed for meiotic hot spot specification are largely unknown. Here we show that the recombinogenic cores of active hot spots in mice harbor several histone H3 and H4 acetylation and methylation marks that are typical of open, active chromatin. Further, deposition of these open chromatin-associated histone marks is dynamic and is manifest at spermatogonia and/or pre-leptotene-stage cells, which facilitates PRDM9 binding and access for Spo11 to direct the formation of DSBs, which are initiated at the leptotene stage. Importantly, manipulating histone acetylase and deacetylase activities established that histone acetylation marks are necessary for both hot spot activity and crossover resolution. We conclude that there are functional roles for histone acetylation marks at mammalian meiotic recombination hot spots.
Department of Cancer Biology, The Scripps Research Institute, Jupiter, Florida, USA igetun@uthsc.edu John.Cleveland@moffitt.org.
Irina V
IV
Getun
Department of Cancer Biology, The Scripps Research Institute, Jupiter, Florida, USA.
Zhen
Z
Wu
Informatics Core, The Scripps Research Institute, Jupiter, Florida, USA.
Mohammad
M
Fallahi
Department of Chemistry, The Scripps Research Institute, Jupiter, Florida, USA.
Souad
S
Ouizem
Department of Chemistry, The Scripps Research Institute, Jupiter, Florida, USA.
Qin
Q
Liu
Department of Cancer Biology, The Scripps Research Institute, Jupiter, Florida, USA.|Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
Weimin
W
Li
Dipartimento di Chimica e Tecnologie del Farmaco, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza Università di Roma, Rome, Italy.
Roberta
R
Costi
Department of Chemistry, The Scripps Research Institute, Jupiter, Florida, USA.
William R
WR
Roush
Department of Cancer Biology, The Scripps Research Institute, Jupiter, Florida, USA igetun@uthsc.edu John.Cleveland@moffitt.org.|Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
John L
JL
Cleveland
Department of Cancer Biology, The Scripps Research Institute, Jupiter, Florida, USA.
Philippe R J
PRJ
Bois
D000818:Animals; D004706:Endodeoxyribonucleases / Q000378:metabolism; D005786:Gene Expression Regulation; D042421:Histone Code; D006657:Histones / Q000378:metabolism; D059765:Homologous Recombination / Q000235:genetics; D008540:Meiosis / Q000235:genetics; D008745:Methylation; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D011418:Prophase / Q000235:genetics; D000099257:Meiotic Recombination Protein SPO11
D004706:Endodeoxyribonucleases; D006657:Histones; D000099257:Meiotic Recombination Protein SPO11
crossover; double-strand break initiation; histone acetylation; meiotic recombination; mouse meiosis