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This article is part of the supplement: Selected articles from the IEEE International Conference on Bioinformatics and Biomedicine 2011: Proteome Science

Open Access Proceedings

Epigenetic functions enriched in transcription factors binding to mouse recombination hotspots

Min Wu1, Chee-Keong Kwoh1, Teresa M Przytycka2, Jing Li3 and Jie Zheng1*

Author Affiliations

1 School of Computer Engineering, Nanyang Technological University, Singapore

2 Computational Biology Branch, NCBI, NLM, National Institutes of Health, USA

3 EECS Department, Case Western Reserve University, USA

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Proteome Science 2012, 10(Suppl 1):S11  doi:10.1186/1477-5956-10-S1-S11

Published: 21 June 2012

Abstract

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 trans-regulator 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.