Title

EWSR1 affects PRDM9-dependent histone 3 methylation and provides a link between recombination hotspots and the chromosome axis protein REC8.

Document Type

Article

Publication Date

1-1-2021

Keywords

JMG

JAX Source

Mol Biol Cell 2021 Jan 1; 32(1):1-14

PMID

33175657

DOI

https://doi.org/10.1091/mbc.e20-09-0604

Grant

GM078452; GM076468; CA034196

Abstract

Meiotic recombination in most mammals requires recombination hotspot activation through the action of the histone 3 Lys-4 and Lys-36 methyltransferase PRDM9 to ensure successful double-strand-break initiation and repair. Here we show that EWSR1, a protein whose role in meiosis was not previously clarified in detail, binds to both PRDM9 and pREC8, a phosphorylated meiosis-specific cohesin, in male meiotic cells. We created a Ewsr1 conditional knockout mouse model to deplete EWSR1 before the onset of meiosis and found that absence of EWSR1 causes meiotic arrest with decreased histone trimethylation at meiotic hotspots, impaired DNA double-strand-break repair, and reduced crossover number. Our results demonstrate that EWSR1 is essential for promoting PRDM9-dependent histone methylation and normal meiotic progress, possibly by facilitating the linking between PRDM9-bound hotspots and the nascent chromosome axis through its component cohesin pREC8.

Comments

We thank Michael Walker for computational help and providing pipelines, Anita Adams and Catrina Spruce for technical help, Mary Ann Handel and Jibak Lee for sharing their antibodies.

This work is dedicated to the memories of Pavlina M. Petkova, a talented scientist and a dear colleague, and Kenneth Paigen, a great scientist, visionary, and friend.

Please contact the Joan Staats Library for information regarding this document.

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