title: PRDM9 interactions with other proteins provide a link between recombination hotspots and the chromosomal axis in meiosis.
abstract: 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.
authors.affiliation: Center for Genome Dynamics, Jackson Laboratory, Bar Harbor, ME 04609.|Department of Biology, Masaryk University, Brno, Czech Republic 625 00.
authors.forename: Emil D
authors.initials: ED
authors.lastname: Parvanov
authors.affiliation: Center for Genome Dynamics, Jackson Laboratory, Bar Harbor, ME 04609.
authors.forename: Hui
authors.initials: H
authors.lastname: Tian
authors.affiliation: Center for Genome Dynamics, Jackson Laboratory, Bar Harbor, ME 04609.
authors.forename: Timothy
authors.initials: T
authors.lastname: Billings
authors.affiliation: Center for Genome Dynamics, Jackson Laboratory, Bar Harbor, ME 04609.
authors.forename: Ruth L
authors.initials: RL
authors.lastname: Saxl
authors.affiliation: Center for Genome Dynamics, Jackson Laboratory, Bar Harbor, ME 04609.
authors.forename: Catrina
authors.initials: C
authors.lastname: Spruce
authors.affiliation: Department of Biology, Masaryk University, Brno, Czech Republic 625 00.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Aithal
authors.affiliation: Department of Biology, Masaryk University, Brno, Czech Republic 625 00 petko.petkov@jax.org lkrejci@chemi.muni.cz.|National Centre for Biomolecular Research, Masaryk University, Brno, Czech Republic 625 00.
authors.forename: Lumir
authors.initials: L
authors.lastname: Krejci
authors.affiliation: Center for Genome Dynamics, Jackson Laboratory, Bar Harbor, ME 04609.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Paigen
authors.affiliation: Center for Genome Dynamics, Jackson Laboratory, Bar Harbor, ME 04609 petko.petkov@jax.org lkrejci@chemi.muni.cz.
authors.forename: Petko M
authors.initials: PM
authors.lastname: Petkov
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism; D002875:Chromosomes / Q000235:genetics / Q000502:physiology*; D004247:DNA / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D016678:Genome; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D059765:Homologous Recombination; D008297:Male; D008540:Meiosis / Q000502:physiology; D051379:Mice; D000072417:Protein Domains; D011995:Recombination, Genetic / Q000502:physiology; D013090:Spermatocytes / Q000378:metabolism
chemical_list: D002843:Chromatin; D004247:DNA; D011495:Histone-Lysine N-Methyltransferase; C544431:PRDM9 protein, human