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bioRxiv · 10.1101/056713

PRDM9 forms a multiprotein complex tethering recombination hotspots to the chromosomal axis

Emil D Parvanov·Hui Tian·Timothy Billings·Ruth L Saxl·Catrina Spruce·Rakesh Aithal·Lumir Krejci·Kenneth Paigen·Petko M Petkov
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Abstract

In mammals, meiotic recombination occurs at 1-2 kb genomic regions termed hotspots, whose positions and activities are determined by PRDM9, a DNA-binding histone methyltransferase. We now 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 co-immunoprecipitation from mouse spermatocytes, we identified four proteins that directly interact with PRDM9s KRAB domain, namely CXXC1, EWSR1, EHMT2, and CDYL. These proteins are co-expressed 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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Emil D Parvanov, Hui Tian, Timothy Billings, Ruth L Saxl, Catrina Spruce, Rakesh Aithal, Lumir Krejci, Kenneth Paigen, Petko M Petkov. 2016-06-02. PRDM9 forms a multiprotein complex tethering recombination hotspots to the chromosomal axis. https://doi.org/10.1101/056713

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