In vivo binding of PRDM9 reveals interactions with noncanonical genomic sites

Corinne Grey; Julie A.J. Clément; Jérôme Buard; Benjamin Leblanc; Ivo Gut; Marta Gut; Laurent Duret; Bernard De Massy

doi:10.1101/gr.217240.116

In vivo binding of PRDM9 reveals interactions with noncanonical genomic sites

Corinne Grey, Julie A.J. Clément, Jérôme Buard, Benjamin Leblanc, Ivo Gut, Marta Gut, Laurent Duret, Bernard De Massy^*

^*Corresponding author for this work

36 Citations (Scopus)

49 Downloads (Pure)

Abstract

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.

Original language	English
Journal	Genome Research
Volume	27
Issue number	4
Pages (from-to)	580-590
Number of pages	11
ISSN	1088-9051
DOIs	https://doi.org/10.1101/gr.217240.116
Publication status	Published - 2017

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In vivo binding of PRDM9 reveals interactions with noncanonical genomic sitesFinal published version, 1.48 MB

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title = "In vivo binding of PRDM9 reveals interactions with noncanonical genomic sites",

abstract = "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.",

author = "Corinne Grey and Cl{\'e}ment, {Julie A.J.} and J{\'e}r{\^o}me Buard and Benjamin Leblanc and Ivo Gut and Marta Gut and Laurent Duret and {De Massy}, Bernard",

year = "2017",

doi = "10.1101/gr.217240.116",

language = "English",

volume = "27",

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TY - JOUR

T1 - In vivo binding of PRDM9 reveals interactions with noncanonical genomic sites

AU - Grey, Corinne

AU - Clément, Julie A.J.

AU - Buard, Jérôme

AU - Leblanc, Benjamin

AU - Gut, Ivo

AU - Gut, Marta

AU - Duret, Laurent

AU - De Massy, Bernard

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

U2 - 10.1101/gr.217240.116

DO - 10.1101/gr.217240.116

M3 - Journal article

C2 - 28336543

AN - SCOPUS:85017542544

SN - 1088-9051

VL - 27

SP - 580

EP - 590

JO - Genome Research

JF - Genome Research

IS - 4

ER -

In vivo binding of PRDM9 reveals interactions with noncanonical genomic sites

Abstract

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