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PRDM9 interactions with other proteins provide a link between recombination hotspots and the chromosomal axis in meiosis

In mammals, meiotic recombination occurs at 1- to 2-kb genomic regions termed hotspots, whose positions and activities are determined by PRDM9, a DNA-binding histone methyltransferase. We show that the KRAB domain of PRDM9 forms complexes with additional proteins to allow hotspots to proceed into th...

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Autores principales: Parvanov, Emil D., Tian, Hui, Billings, Timothy, Saxl, Ruth L., Spruce, Catrina, Aithal, Rakesh, Krejci, Lumir, Paigen, Kenneth, Petkov, Petko M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341731/
https://www.ncbi.nlm.nih.gov/pubmed/27932493
http://dx.doi.org/10.1091/mbc.E16-09-0686
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author Parvanov, Emil D.
Tian, Hui
Billings, Timothy
Saxl, Ruth L.
Spruce, Catrina
Aithal, Rakesh
Krejci, Lumir
Paigen, Kenneth
Petkov, Petko M.
author_facet Parvanov, Emil D.
Tian, Hui
Billings, Timothy
Saxl, Ruth L.
Spruce, Catrina
Aithal, Rakesh
Krejci, Lumir
Paigen, Kenneth
Petkov, Petko M.
author_sort Parvanov, Emil D.
collection PubMed
description In mammals, meiotic recombination occurs at 1- to 2-kb genomic regions termed hotspots, whose positions and activities are determined by PRDM9, a DNA-binding histone methyltransferase. We show that the KRAB domain of PRDM9 forms complexes with additional proteins to allow hotspots to proceed into the next phase of recombination. By a combination of yeast-two hybrid assay, in vitro binding, and coimmunoprecipitation from mouse spermatocytes, we identified four proteins that directly interact with PRDM9’s KRAB domain, namely CXXC1, EWSR1, EHMT2, and CDYL. These proteins are coexpressed in spermatocytes at the early stages of meiotic prophase I, the limited period when PRDM9 is expressed. We also detected association of PRDM9-bound complexes with the meiotic cohesin REC8 and the synaptonemal complex proteins SYCP3 and SYCP1. Our results suggest a model in which PRDM9-bound hotspot DNA is brought to the chromosomal axis by the action of these proteins, ensuring the proper chromatin and spatial environment for subsequent recombination events.
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spelling pubmed-53417312017-04-16 PRDM9 interactions with other proteins provide a link between recombination hotspots and the chromosomal axis in meiosis Parvanov, Emil D. Tian, Hui Billings, Timothy Saxl, Ruth L. Spruce, Catrina Aithal, Rakesh Krejci, Lumir Paigen, Kenneth Petkov, Petko M. Mol Biol Cell Articles In mammals, meiotic recombination occurs at 1- to 2-kb genomic regions termed hotspots, whose positions and activities are determined by PRDM9, a DNA-binding histone methyltransferase. We show that the KRAB domain of PRDM9 forms complexes with additional proteins to allow hotspots to proceed into the next phase of recombination. By a combination of yeast-two hybrid assay, in vitro binding, and coimmunoprecipitation from mouse spermatocytes, we identified four proteins that directly interact with PRDM9’s KRAB domain, namely CXXC1, EWSR1, EHMT2, and CDYL. These proteins are coexpressed in spermatocytes at the early stages of meiotic prophase I, the limited period when PRDM9 is expressed. We also detected association of PRDM9-bound complexes with the meiotic cohesin REC8 and the synaptonemal complex proteins SYCP3 and SYCP1. Our results suggest a model in which PRDM9-bound hotspot DNA is brought to the chromosomal axis by the action of these proteins, ensuring the proper chromatin and spatial environment for subsequent recombination events. The American Society for Cell Biology 2017-02-01 /pmc/articles/PMC5341731/ /pubmed/27932493 http://dx.doi.org/10.1091/mbc.E16-09-0686 Text en © 2017 Parvanov et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Parvanov, Emil D.
Tian, Hui
Billings, Timothy
Saxl, Ruth L.
Spruce, Catrina
Aithal, Rakesh
Krejci, Lumir
Paigen, Kenneth
Petkov, Petko M.
PRDM9 interactions with other proteins provide a link between recombination hotspots and the chromosomal axis in meiosis
title PRDM9 interactions with other proteins provide a link between recombination hotspots and the chromosomal axis in meiosis
title_full PRDM9 interactions with other proteins provide a link between recombination hotspots and the chromosomal axis in meiosis
title_fullStr PRDM9 interactions with other proteins provide a link between recombination hotspots and the chromosomal axis in meiosis
title_full_unstemmed PRDM9 interactions with other proteins provide a link between recombination hotspots and the chromosomal axis in meiosis
title_short PRDM9 interactions with other proteins provide a link between recombination hotspots and the chromosomal axis in meiosis
title_sort prdm9 interactions with other proteins provide a link between recombination hotspots and the chromosomal axis in meiosis
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341731/
https://www.ncbi.nlm.nih.gov/pubmed/27932493
http://dx.doi.org/10.1091/mbc.E16-09-0686
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