Mouse PRDM9 DNA-binding specificity determines sites of histone H3 lysine 4 trimethylation for initiation of meiotic recombination.

Meiotic recombination generates reciprocal exchanges between homologous chromosomes (also called crossovers, COs) that are essential for proper chromosome segregation during meiosis and are a major source of genome diversity by generating new allele combinations. COs have two striking properties: th...

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Autores principales:	Corinne Grey, Pauline Barthès, Gaëlle Chauveau-Le Friec, Francina Langa, Frédéric Baudat, Bernard de Massy
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/3ba0c3f951d740a3beea6fcdfa7c67d7
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spelling	oai:doaj.org-article:3ba0c3f951d740a3beea6fcdfa7c67d72021-11-18T05:36:56ZMouse PRDM9 DNA-binding specificity determines sites of histone H3 lysine 4 trimethylation for initiation of meiotic recombination.1544-91731545-788510.1371/journal.pbio.1001176https://doaj.org/article/3ba0c3f951d740a3beea6fcdfa7c67d72011-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22028627/pdf/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Meiotic recombination generates reciprocal exchanges between homologous chromosomes (also called crossovers, COs) that are essential for proper chromosome segregation during meiosis and are a major source of genome diversity by generating new allele combinations. COs have two striking properties: they occur at specific sites, called hotspots, and these sites evolve rapidly. In mammals, the Prdm9 gene, which encodes a meiosis-specific histone H3 methyltransferase, has recently been identified as a determinant of CO hotspots. Here, using transgenic mice, we show that the sole modification of PRDM9 zinc fingers leads to changes in hotspot activity, histone H3 lysine 4 trimethylation (H3K4me3) levels, and chromosome-wide distribution of COs. We further demonstrate by an in vitro assay that the PRDM9 variant associated with hotspot activity binds specifically to DNA sequences located at the center of the three hotspots tested. Remarkably, we show that mutations in cis located at hotspot centers and associated with a decrease of hotspot activity affect PRDM9 binding. Taken together, these results provide the direct demonstration that Prdm9 is a master regulator of hotspot localization through the DNA binding specificity of its zinc finger array and that binding of PRDM9 at hotspots promotes local H3K4me3 enrichment.Corinne GreyPauline BarthèsGaëlle Chauveau-Le FriecFrancina LangaFrédéric BaudatBernard de MassyPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 9, Iss 10, p e1001176 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Corinne Grey Pauline Barthès Gaëlle Chauveau-Le Friec Francina Langa Frédéric Baudat Bernard de Massy Mouse PRDM9 DNA-binding specificity determines sites of histone H3 lysine 4 trimethylation for initiation of meiotic recombination.
description	Meiotic recombination generates reciprocal exchanges between homologous chromosomes (also called crossovers, COs) that are essential for proper chromosome segregation during meiosis and are a major source of genome diversity by generating new allele combinations. COs have two striking properties: they occur at specific sites, called hotspots, and these sites evolve rapidly. In mammals, the Prdm9 gene, which encodes a meiosis-specific histone H3 methyltransferase, has recently been identified as a determinant of CO hotspots. Here, using transgenic mice, we show that the sole modification of PRDM9 zinc fingers leads to changes in hotspot activity, histone H3 lysine 4 trimethylation (H3K4me3) levels, and chromosome-wide distribution of COs. We further demonstrate by an in vitro assay that the PRDM9 variant associated with hotspot activity binds specifically to DNA sequences located at the center of the three hotspots tested. Remarkably, we show that mutations in cis located at hotspot centers and associated with a decrease of hotspot activity affect PRDM9 binding. Taken together, these results provide the direct demonstration that Prdm9 is a master regulator of hotspot localization through the DNA binding specificity of its zinc finger array and that binding of PRDM9 at hotspots promotes local H3K4me3 enrichment.
format	article
author	Corinne Grey Pauline Barthès Gaëlle Chauveau-Le Friec Francina Langa Frédéric Baudat Bernard de Massy
author_facet	Corinne Grey Pauline Barthès Gaëlle Chauveau-Le Friec Francina Langa Frédéric Baudat Bernard de Massy
author_sort	Corinne Grey
title	Mouse PRDM9 DNA-binding specificity determines sites of histone H3 lysine 4 trimethylation for initiation of meiotic recombination.
title_short	Mouse PRDM9 DNA-binding specificity determines sites of histone H3 lysine 4 trimethylation for initiation of meiotic recombination.
title_full	Mouse PRDM9 DNA-binding specificity determines sites of histone H3 lysine 4 trimethylation for initiation of meiotic recombination.
title_fullStr	Mouse PRDM9 DNA-binding specificity determines sites of histone H3 lysine 4 trimethylation for initiation of meiotic recombination.
title_full_unstemmed	Mouse PRDM9 DNA-binding specificity determines sites of histone H3 lysine 4 trimethylation for initiation of meiotic recombination.
title_sort	mouse prdm9 dna-binding specificity determines sites of histone h3 lysine 4 trimethylation for initiation of meiotic recombination.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/3ba0c3f951d740a3beea6fcdfa7c67d7
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Mouse PRDM9 DNA-binding specificity determines sites of histone H3 lysine 4 trimethylation for initiation of meiotic recombination.

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