Scale matters: The spatial correlation of yeast meiotic DNA breaks with histone H3 trimethylation is driven largely by independent colocalization at promoters Journal Article


Authors: Tischfield, S. E.; Keeney, S.
Article Title: Scale matters: The spatial correlation of yeast meiotic DNA breaks with histone H3 trimethylation is driven largely by independent colocalization at promoters
Abstract: During meiosis in many organisms, homologous chromosomes engage in numerous recombination events initiated by DNA double-strand breaks (DSBs) formed by the Spo11 protein. DSBs are distributed nonrandomly, which governs how recombination influences inheritance and genome evolution. The chromosomal features that shape DSB distribution are not well understood. In the budding yeast Saccharomyces cerevisiae, trimethylation of lysine 4 of histone H3 (H3K4me3) has been suggested to play a causal role in targeting Spo11 activity to small regions of preferred DSB formation called hotspots. The link between H3K4me3 and DSBs is supported in part by a genome-wide spatial correlation between the two. However, this correlation has only been evaluated using relatively low-resolution maps of DSBs, H3K4me3 or both. These maps illuminate chromosomal features that influence DSB distributions on a large scale (several kb and greater) but do not adequately resolve features, such as chromatin structure, that act on finer scales (kb and shorter). Using recent nucleotide-resolution maps of DSBs and meiotic chromatin structure, we find that the previously described spatial correlation between H3K4me3 and DSB hotspots is principally attributable to coincident localization of both to gene promoters. Once proximity to the nucleosome-depleted regions in promoters is accounted for, H3K4me3 status has only modest predictive power for determining DSB frequency or location. This analysis provides a cautionary tale about the importance of scale in genome-wide analyses of DSB and recombination patterns. © 2012 Landes Bioscience.
Keywords: methylation; review; nonhuman; protein localization; chromosome; meiosis; genome analysis; correlation analysis; saccharomyces cerevisiae; chromatin; histone-lysine n-methyltransferase; promoter regions, genetic; recombination, genetic; histone h3; dna breaks, double-stranded; double stranded dna break; saccharomyces cerevisiae proteins; saccharomycetales; histones; protein methylation; chromosomes, fungal; chromatin structure; double-strand breaks; endodeoxyribonucleases; recombination; spo11; h3k4 trimethylation; set1
Journal Title: Cell Cycle
Volume: 11
Issue: 8
ISSN: 1538-4101
Publisher: Taylor & Francis Inc.  
Date Published: 2012-04-15
Start Page: 1496
End Page: 1503
Language: English
DOI: 10.4161/cc.19733
PROVIDER: scopus
PMCID: PMC3341227
PUBMED: 22433953
DOI/URL:
Notes: --- - "Export Date: 4 June 2012" - "Source: Scopus"
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  1. Scott N Keeney
    138 Keeney