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EWSR1 Regulates PRDM9-Dependent Histone 3 Methylation and Links Recombination Hotspots With the Chromosomal Axis

36 Pages Posted: 4 Apr 2018 Sneak Peek Status: Review Complete

See all articles by Hui Tian

Hui Tian

The Jackson Laboratory

Timothy Billings

The Jackson Laboratory

Michael Walker

The Jackson Laboratory

Pavlina M. Petkova

The Jackson Laboratory

Christopher L. Baker

The Jackson Laboratory

Petko M. Petkov

The Jackson Laboratory

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Abstract

Meiotic recombination in most mammals requires recombination hotspot activation through the action of the histone 3 lysine-4 and lysine-36 methyltransferase PRDM9 to ensure successful double-strand break initiation and repair. Here we show that EWSR1, a protein with a previously uncharacterized role in meiosis, binds to PRDM9 and increases the efficiency of trimethylation at hotspots in vivo. Additionally, EWSR1 links PRDM9-activated hotspots and the nascent chromosomal axis through the phosphorylated meiotic-specific cohesin REC8. Together, these two functions of EWSR1 direct the choice of which hotspots will be used for double-strand break formation and repair, assuring that a sufficient number of crossovers are properly positioned along the centromere-telomere axis. These results show that successful recombination and meiosis require proper association of activated hotspots with the chromosomal axis mediated by interactions between EWSR1, PRDM9, and pREC8.

Suggested Citation

Tian, Hui and Billings, Timothy and Walker, Michael and Petkova, Pavlina M. and Baker, Christopher L. and Petkov, Petko M., EWSR1 Regulates PRDM9-Dependent Histone 3 Methylation and Links Recombination Hotspots With the Chromosomal Axis (2018). Available at SSRN: https://ssrn.com/abstract=3155549 or http://dx.doi.org/10.2139/ssrn.3155549
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Hui Tian (Contact Author)

The Jackson Laboratory

600 Main Street
Bar Harbor, ME 04609
United States

Timothy Billings

The Jackson Laboratory

600 Main Street
Bar Harbor, ME 04609
United States

Michael Walker

The Jackson Laboratory

600 Main Street
Bar Harbor, ME 04609
United States

Pavlina M. Petkova

The Jackson Laboratory

600 Main Street
Bar Harbor, ME 04609
United States

Christopher L. Baker

The Jackson Laboratory

600 Main Street
Bar Harbor, ME 04609
United States

Petko M. Petkov

The Jackson Laboratory

600 Main Street
Bar Harbor, ME 04609
United States

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