The PRDM9 KRAB domain is required for meiosis and involved in protein interactions

Chromosoma
Yukiko ImaiBernard de Massy

Abstract

PR domain-containing protein 9 (PRDM9) is a major regulator of the localization of meiotic recombination hotspots in the human and mouse genomes. This role involves its DNA-binding domain, which is composed of a tandem array of zinc fingers, and PRDM9-dependent trimethylation of histone H3 at lysine 4. PRDM9 is a member of the PRDM family of transcription regulators, but unlike other family members, it contains a Krüppel-associated box (KRAB)-related domain that is predicted to be a potential protein interaction domain. Here, we show that truncation of the KRAB domain of mouse PRDM9 leads to loss of PRDM9 function and altered meiotic prophase and gametogenesis. In addition, we identified proteins that interact with the KRAB domain of PRDM9 in yeast two-hybrid assay screens, particularly CXXC1, a member of the COMPASS complex. We also show that CXXC1 interacts with IHO1, an essential component of the meiotic double-strand break (DSB) machinery. As CXXC1 is orthologous to Saccharomyces cerevisiae Spp1 that links DSB sites to the DSB machinery on the chromosome axis, we propose that these molecular interactions involved in the regulation of meiotic DSB formation are conserved in mouse meiosis.

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Citations

Oct 11, 2017·Journal of Experimental Botany·Emma J LawrenceIan R Henderson
Jul 3, 2018·Cell Cycle·Agnieszka LukaszewiczMaria Jasin
Aug 31, 2018·PLoS Genetics·Corinne GreyBernard de Massy
Nov 8, 2017·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Irene Tiemann-BoegeAngelika Heissl
Feb 1, 2018·Biology of Reproduction·Ewelina Bolcun-Filas, Mary Ann Handel
Dec 19, 2019·Nature Communications·Abdellah Allali-HassaniMasoud Vedadi
Sep 14, 2019·Annual Review of Genetics·Melania BrunoTodd S Macfarlan
Jan 12, 2020·Molecular Biology and Evolution·Drew R SchieldTodd A Castoe
Jan 26, 2018·Trends in Genetics : TIG·Kenneth Paigen, Petko M Petkov
Apr 21, 2018·Genetics·Sarah Thibault-SennettGalina V Petukhova
Jul 29, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yidai YangJean-Francois Couture
Nov 23, 2021·Frontiers in Cell and Developmental Biology·Benjamin AllevaRafael Daniel Camerini-Otero

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Methods Mentioned

BETA
two-hybrid
ChIP
Y2H
RNA-seq
co-immunoprecipitation
Protein Assay
immunoprecipitation
PCR

Software Mentioned

Coffee
NDP
CellProfiler
BoxShade
Image Lab
OMERO
ZEN
view2
ImageJ

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