TY - JOUR T1 - PRDM9 forms a multiprotein complex tethering recombination hotspots to the chromosomal axis JF - bioRxiv DO - 10.1101/056713 SP - 056713 AU - Emil D. Parvanov AU - Hui Tian AU - Timothy Billings AU - Ruth L. Saxl AU - Catrina Spruce AU - Rakesh Aithal AU - Lumir Krejci AU - Kenneth Paigen AU - Petko M. Petkov Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/09/16/056713.abstract N2 - 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 PRDM9’s 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. ER -