Publication details

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

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Authors

PARVANOV Emil Damyanov TIAN Hui BILLINGS Timothy SAXL Ruth L. SPRUCE Catrina AITHAL Rakesh KREJČÍ Lumír PAIGEN Kenneth PETKOV Petko M.

Year of publication 2017
Type Article in Periodical
Magazine / Source Molecular Biology of the Cell
MU Faculty or unit

Faculty of Medicine

Citation
Doi http://dx.doi.org/10.1091/mbc.E16-09-0686
Field Genetics and molecular biology
Keywords CXXC FINGER PROTEIN-1; MEIOTIC RECOMBINATION; HISTONE METHYLTRANSFERASES; CHROMATIN MODIFICATIONS; BIOLOGICAL FUNCTIONS; GENE REARRANGEMENTS; ANALYSIS REVEALS; EWING SARCOMA; HOT-SPOTS; METHYLATION
Description 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.
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