Hotspot mapping quantifies the contribution of PRDM9 to meiotic DSB localization

Monday, October 24, 2011 — Poster Session I
Noon – 2:00 p.m.	Natcher Conference Center	NIDDK	BIOINFO-3

Authors

• K Brick
• F Smagulova
• P Khil
• G Petukhova
• RD Camerini-Otero

Abstract

The genetic and molecular determinants of double strand break (DSBs) locations in meiosis remain an enigma. In mammals, meiotic DSBs and subsequent recombination are known to occur primarily at defined genomic loci called hotspots and recently, we generated the first physical genome-wide map of hotspots in a mammalian genome. We subsequently showed that almost all hotspots were associated with testis-specific H3K4me3 chromatin marks which are likely introduced by the meiosis-specific histone-methyltransferase, PRDM9. This protein plays a role both in speciation and in regulating recombination rate. We sought to conclusively address the contribution of PRDM9 to DSB localization by mapping hotspots in different mouse strains. Strains sharing a prdm9 allele had virtually identical hotspot distributions however no overlap was observed in congenic strains with different alleles. In F1 progeny of these congenic mice, one prdm9 allele showed incomplete dominance as ~75% of F1 hotspots were associated with this allele. Hotspots for each prdm9 allele had different associated sequence motifs, each of which reflected the predicted DNA binding site for the representative allele. Intriguingly, many hotspots in the pseudo-autosomal region and its flanking region were prdm9 independent showing that an alternative mechanism governs break formation in this region.

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