Unbiased, Genome-Wide In Vivo Mapping of Transcriptional Regulatory Elements Reveals Sex Differences in Chromatin Structure Associated with Sex-Specific Liver Gene Expression
We have used a simple and efficient method to identify condition-specific transcriptional regulatory sites in vivo to help elucidate the molecular basis of sex-related differences in transcription, which are widespread in mammalian tissues and affect normal physiology, drug response, inflammation, a...
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| Format: | Article |
| Language: | en_US |
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American Society for Microbiology
2010
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| Online Access: | http://hdl.handle.net/1721.1/60028 https://orcid.org/0000-0001-9249-8181 |
| _version_ | 1826207281084104704 |
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| author | Ling, Guoyu Sugathan, Aarathi Mazor, Tali Fraenkel, Ernest |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Ling, Guoyu Sugathan, Aarathi Mazor, Tali Fraenkel, Ernest |
| author_sort | Ling, Guoyu |
| collection | MIT |
| description | We have used a simple and efficient method to identify condition-specific transcriptional regulatory sites in vivo to help elucidate the molecular basis of sex-related differences in transcription, which are widespread in mammalian tissues and affect normal physiology, drug response, inflammation, and disease. To systematically uncover transcriptional regulators responsible for these differences, we used DNase hypersensitivity analysis coupled with high-throughput sequencing to produce condition-specific maps of regulatory sites in male and female mouse livers and in livers of male mice feminized by continuous infusion of growth hormone (GH). We identified 71,264 hypersensitive sites, with 1,284 showing robust sex-related differences. Continuous GH infusion suppressed the vast majority of male-specific sites and induced a subset of female-specific sites in male livers. We also identified broad genomic regions (up to ~100 kb) showing sex-dependent hypersensitivity and similar patterns of GH responses. We found a strong association of sex-specific sites with sex-specific transcription; however, a majority of sex-specific sites were >100 kb from sex-specific genes. By analyzing sequence motifs within regulatory regions, we identified two known regulators of liver sexual dimorphism and several new candidates for further investigation. This approach can readily be applied to mapping condition-specific regulatory sites in mammalian tissues under a wide variety of physiological conditions. |
| first_indexed | 2024-09-23T13:47:13Z |
| format | Article |
| id | mit-1721.1/60028 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:47:13Z |
| publishDate | 2010 |
| publisher | American Society for Microbiology |
| record_format | dspace |
| spelling | mit-1721.1/600282022-09-28T16:09:47Z Unbiased, Genome-Wide In Vivo Mapping of Transcriptional Regulatory Elements Reveals Sex Differences in Chromatin Structure Associated with Sex-Specific Liver Gene Expression Ling, Guoyu Sugathan, Aarathi Mazor, Tali Fraenkel, Ernest Massachusetts Institute of Technology. Department of Biological Engineering Fraenkel, Ernest Mazor, Tali Fraenkel, Ernest We have used a simple and efficient method to identify condition-specific transcriptional regulatory sites in vivo to help elucidate the molecular basis of sex-related differences in transcription, which are widespread in mammalian tissues and affect normal physiology, drug response, inflammation, and disease. To systematically uncover transcriptional regulators responsible for these differences, we used DNase hypersensitivity analysis coupled with high-throughput sequencing to produce condition-specific maps of regulatory sites in male and female mouse livers and in livers of male mice feminized by continuous infusion of growth hormone (GH). We identified 71,264 hypersensitive sites, with 1,284 showing robust sex-related differences. Continuous GH infusion suppressed the vast majority of male-specific sites and induced a subset of female-specific sites in male livers. We also identified broad genomic regions (up to ~100 kb) showing sex-dependent hypersensitivity and similar patterns of GH responses. We found a strong association of sex-specific sites with sex-specific transcription; however, a majority of sex-specific sites were >100 kb from sex-specific genes. By analyzing sequence motifs within regulatory regions, we identified two known regulators of liver sexual dimorphism and several new candidates for further investigation. This approach can readily be applied to mapping condition-specific regulatory sites in mammalian tissues under a wide variety of physiological conditions. National Institutes of Health (U.S) ( DK33765) National Institutes of Health (U.S) (grant 577 5 P42 ES07381) 2010-11-23T14:13:17Z 2010-11-23T14:13:17Z 2010-09 2010-05 Article http://purl.org/eprint/type/JournalArticle 0270-7306 http://hdl.handle.net/1721.1/60028 Ling, Guoyu et al. “Unbiased, Genome-Wide In Vivo Mapping of Transcriptional Regulatory Elements Reveals Sex Differences in Chromatin Structure Associated with Sex-Specific Liver Gene Expression.” Molecular and Cellular Biology 30.23 (2010): 5531-5544. 20876297 https://orcid.org/0000-0001-9249-8181 en_US http://dx.doi.org/10.1128/MCB.00601-10 Molecular and Cellular Biology application/pdf American Society for Microbiology Howard Silver |
| spellingShingle | Ling, Guoyu Sugathan, Aarathi Mazor, Tali Fraenkel, Ernest Unbiased, Genome-Wide In Vivo Mapping of Transcriptional Regulatory Elements Reveals Sex Differences in Chromatin Structure Associated with Sex-Specific Liver Gene Expression |
| title | Unbiased, Genome-Wide In Vivo Mapping of Transcriptional Regulatory Elements Reveals Sex Differences in Chromatin Structure Associated with Sex-Specific Liver Gene Expression |
| title_full | Unbiased, Genome-Wide In Vivo Mapping of Transcriptional Regulatory Elements Reveals Sex Differences in Chromatin Structure Associated with Sex-Specific Liver Gene Expression |
| title_fullStr | Unbiased, Genome-Wide In Vivo Mapping of Transcriptional Regulatory Elements Reveals Sex Differences in Chromatin Structure Associated with Sex-Specific Liver Gene Expression |
| title_full_unstemmed | Unbiased, Genome-Wide In Vivo Mapping of Transcriptional Regulatory Elements Reveals Sex Differences in Chromatin Structure Associated with Sex-Specific Liver Gene Expression |
| title_short | Unbiased, Genome-Wide In Vivo Mapping of Transcriptional Regulatory Elements Reveals Sex Differences in Chromatin Structure Associated with Sex-Specific Liver Gene Expression |
| title_sort | unbiased genome wide in vivo mapping of transcriptional regulatory elements reveals sex differences in chromatin structure associated with sex specific liver gene expression |
| url | http://hdl.handle.net/1721.1/60028 https://orcid.org/0000-0001-9249-8181 |
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