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In vivo binding of PRDM9 reveals interactions with noncanonical genomic sites

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 extensiv...

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Autores principales: Grey, Corinne, Clément, Julie A.J., Buard, Jérôme, Leblanc, Benjamin, Gut, Ivo, Gut, Marta, Duret, Laurent, de Massy, Bernard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378176/
https://www.ncbi.nlm.nih.gov/pubmed/28336543
http://dx.doi.org/10.1101/gr.217240.116
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author Grey, Corinne
Clément, Julie A.J.
Buard, Jérôme
Leblanc, Benjamin
Gut, Ivo
Gut, Marta
Duret, Laurent
de Massy, Bernard
author_facet Grey, Corinne
Clément, Julie A.J.
Buard, Jérôme
Leblanc, Benjamin
Gut, Ivo
Gut, Marta
Duret, Laurent
de Massy, Bernard
author_sort Grey, Corinne
collection PubMed
description 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.
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spelling pubmed-53781762017-04-12 In vivo binding of PRDM9 reveals interactions with noncanonical genomic sites Grey, Corinne Clément, Julie A.J. Buard, Jérôme Leblanc, Benjamin Gut, Ivo Gut, Marta Duret, Laurent de Massy, Bernard Genome Res Research 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. Cold Spring Harbor Laboratory Press 2017-04 /pmc/articles/PMC5378176/ /pubmed/28336543 http://dx.doi.org/10.1101/gr.217240.116 Text en © 2017 Grey et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by/4.0/ This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
spellingShingle Research
Grey, Corinne
Clément, Julie A.J.
Buard, Jérôme
Leblanc, Benjamin
Gut, Ivo
Gut, Marta
Duret, Laurent
de Massy, Bernard
In vivo binding of PRDM9 reveals interactions with noncanonical genomic sites
title In vivo binding of PRDM9 reveals interactions with noncanonical genomic sites
title_full In vivo binding of PRDM9 reveals interactions with noncanonical genomic sites
title_fullStr In vivo binding of PRDM9 reveals interactions with noncanonical genomic sites
title_full_unstemmed In vivo binding of PRDM9 reveals interactions with noncanonical genomic sites
title_short In vivo binding of PRDM9 reveals interactions with noncanonical genomic sites
title_sort in vivo binding of prdm9 reveals interactions with noncanonical genomic sites
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378176/
https://www.ncbi.nlm.nih.gov/pubmed/28336543
http://dx.doi.org/10.1101/gr.217240.116
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