Prediction of trans-regulators of recombination hotspots in mouse genome
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 "reco...
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| Format: | Conference Paper |
| Language: | English |
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2013
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| Online Access: | https://hdl.handle.net/10356/96527 http://hdl.handle.net/10220/17350 |
| _version_ | 1826115035773009920 |
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| author | Przytycka, Teresa M. Wu, Min Kwoh, Chee Keong Li, Jing Zheng, Jie |
| author2 | School of Chemical and Biomedical Engineering |
| author_facet | School of Chemical and Biomedical Engineering Przytycka, Teresa M. Wu, Min Kwoh, Chee Keong Li, Jing Zheng, Jie |
| author_sort | Przytycka, Teresa M. |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T03:48:57Z |
| format | Conference Paper |
| id | ntu-10356/96527 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:48:57Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | ntu-10356/965272020-03-07T11:48:47Z Prediction of trans-regulators of recombination hotspots in mouse genome Przytycka, Teresa M. Wu, Min Kwoh, Chee Keong Li, Jing Zheng, Jie School of Chemical and Biomedical Engineering IEEE International Conference on Bioinformatics and Biomedicine (2011 : Atlanta, US) DRNTU::Science::Medicine::Biomedical engineering 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. MOE (Min. of Education, S’pore) Accepted version 2013-11-06T07:26:19Z 2019-12-06T19:31:51Z 2013-11-06T07:26:19Z 2019-12-06T19:31:51Z 2011 2011 Conference Paper Wu, M., Kwoh, C. K., Przytycka, T. M., Li, J., & Zheng, J. (2011). Prediction of trans-regulators of recombination hotspots in mouse genome. 2011 IEEE International Conference on Bioinformatics and Biomedicine, pp57-62. https://hdl.handle.net/10356/96527 http://hdl.handle.net/10220/17350 10.1109/BIBM.2011.77 en © 2011 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works. The published version is available at: [http://dx.doi.org/10.1109/BIBM.2011.77] application/pdf |
| spellingShingle | DRNTU::Science::Medicine::Biomedical engineering Przytycka, Teresa M. Wu, Min Kwoh, Chee Keong Li, Jing Zheng, Jie Prediction of trans-regulators of recombination hotspots in mouse genome |
| title | Prediction of trans-regulators of recombination hotspots in mouse genome |
| title_full | Prediction of trans-regulators of recombination hotspots in mouse genome |
| title_fullStr | Prediction of trans-regulators of recombination hotspots in mouse genome |
| title_full_unstemmed | Prediction of trans-regulators of recombination hotspots in mouse genome |
| title_short | Prediction of trans-regulators of recombination hotspots in mouse genome |
| title_sort | prediction of trans regulators of recombination hotspots in mouse genome |
| topic | DRNTU::Science::Medicine::Biomedical engineering |
| url | https://hdl.handle.net/10356/96527 http://hdl.handle.net/10220/17350 |
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