PRDM9 interactions with other proteins provide a link between recombination hotspots and the chromosomal axis in meiosis
| Authors | |
|---|---|
| Year of publication | 2017 |
| Type | Article in Periodical |
| Magazine / Source | Molecular Biology of the Cell |
| MU Faculty or unit | |
| 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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