Document Detail

Scale matters: the spatial correlation of yeast meiotic DNA breaks with histone H3 trimethylation is driven largely by independent colocalization at promoters.
MedLine Citation:
PMID:  22433953     Owner:  NLM     Status:  MEDLINE    
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.
Sam E Tischfield; Scott Keeney
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-04-15
Journal Detail:
Title:  Cell cycle (Georgetown, Tex.)     Volume:  11     ISSN:  1551-4005     ISO Abbreviation:  Cell Cycle     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-30     Completed Date:  2012-09-14     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  101137841     Medline TA:  Cell Cycle     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1496-503     Citation Subset:  IM    
Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
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MeSH Terms
Chromatin / chemistry,  metabolism
Chromosomes, Fungal / metabolism
DNA Breaks, Double-Stranded
Endodeoxyribonucleases / metabolism
Histone-Lysine N-Methyltransferase / metabolism
Histones / genetics*,  metabolism
Promoter Regions, Genetic*
Recombination, Genetic
Saccharomyces cerevisiae / metabolism*
Saccharomyces cerevisiae Proteins / genetics,  metabolism
Grant Support
R01 GM058673/GM/NIGMS NIH HHS; R01 GM058673/GM/NIGMS NIH HHS; //Howard Hughes Medical Institute
Reg. No./Substance:
0/Chromatin; 0/Histones; 0/Saccharomyces cerevisiae Proteins; EC N-Methyltransferase; EC protein, S cerevisiae; EC 3.1.-/Endodeoxyribonucleases; EC 3.1.-/Spo11 protein, S cerevisiae

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