Epigenetic functions enriched in transcription factors binding to mouse recombination hotspots

The regulatory mechanism of recombination is a fundamental problem in genomics,with wide applications in genome-wide association studies,birth-defect diseases,molecular evolution,cancer research,etc. in mammalian genomes,recombination events cluster into short genomic regions called recombination hotspots. recently,a 13- mer motif enriched in hotspots is identified as a candidate cis-regulatory element of human recombination hotspots; moreover,a zinc finger protein,prdm9,binds to this motif and is associated with variation of recombination phenotype in human and mouse genomes,thus is a trans-acting regulator of recombination hotspots. however,this pair of cis and trans-regulators covers only a fraction of hotspots,thus other regulators of recombination hotspots remain to be discovered. in this paper,we propose an approach to predicting additional trans-regulators from dna-binding proteins by comparing their enrichment of binding sites in hotspots. applying this approach on newly mapped mouse hotspots genome-wide,we confirmed that prdm9 is a major transregulator of hotspots. in addition,a list of top candidate trans-regulators of mouse hotspots is reported. using go analysis we observed that the top genes are enriched with function of histone modification,highlighting the epigenetic regulatory mechanisms of recombination hotspots. © 2012 wu et al.