Genome-Wide Location Analysis Reveals Distinct Transcriptional Circuitry by Paralogous Regulators Foxa1 and Foxa2
Gene duplication is a powerful driver of evolution. Newly duplicated genes acquire new roles that are relevant to fitness, or they will be lost over time. A potential path to functional relevance is mutation of the coding sequence leading to the acquisition of novel biochemical properties, as analyz...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | en_US |
| Published: |
Public Library of Science
2012
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| Online Access: | http://hdl.handle.net/1721.1/73529 |
| _version_ | 1811078652543107072 |
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| author | Bochkis, Irina M. Schug, Jonathan Ye, Diana Z. Kurinna, Svitlana Stratton, Sabrina A. Barton, Michelle C. Kaestner, Klaus H. |
| author2 | Bochkis, Irina M. |
| author_facet | Bochkis, Irina M. Bochkis, Irina M. Schug, Jonathan Ye, Diana Z. Kurinna, Svitlana Stratton, Sabrina A. Barton, Michelle C. Kaestner, Klaus H. |
| author_sort | Bochkis, Irina M. |
| collection | MIT |
| description | Gene duplication is a powerful driver of evolution. Newly duplicated genes acquire new roles that are relevant to fitness, or they will be lost over time. A potential path to functional relevance is mutation of the coding sequence leading to the acquisition of novel biochemical properties, as analyzed here for the highly homologous paralogs Foxa1 and Foxa2 transcriptional regulators. We determine by genome-wide location analysis (ChIP-Seq) that, although Foxa1 and Foxa2 share a large fraction of binding sites in the liver, each protein also occupies distinct regulatory elements in vivo. Foxa1-only sites are enriched for p53 binding sites and are frequently found near genes important to cell cycle regulation, while Foxa2-restricted sites show only a limited match to the forkhead consensus and are found in genes involved in steroid and lipid metabolism. Thus, Foxa1 and Foxa2, while redundant during development, have evolved divergent roles in the adult liver, ensuring the maintenance of both genes during evolution. |
| first_indexed | 2024-09-23T11:03:31Z |
| format | Article |
| id | mit-1721.1/73529 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:03:31Z |
| publishDate | 2012 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/735292022-10-01T00:50:38Z Genome-Wide Location Analysis Reveals Distinct Transcriptional Circuitry by Paralogous Regulators Foxa1 and Foxa2 Bochkis, Irina M. Schug, Jonathan Ye, Diana Z. Kurinna, Svitlana Stratton, Sabrina A. Barton, Michelle C. Kaestner, Klaus H. Bochkis, Irina M. Gene duplication is a powerful driver of evolution. Newly duplicated genes acquire new roles that are relevant to fitness, or they will be lost over time. A potential path to functional relevance is mutation of the coding sequence leading to the acquisition of novel biochemical properties, as analyzed here for the highly homologous paralogs Foxa1 and Foxa2 transcriptional regulators. We determine by genome-wide location analysis (ChIP-Seq) that, although Foxa1 and Foxa2 share a large fraction of binding sites in the liver, each protein also occupies distinct regulatory elements in vivo. Foxa1-only sites are enriched for p53 binding sites and are frequently found near genes important to cell cycle regulation, while Foxa2-restricted sites show only a limited match to the forkhead consensus and are found in genes involved in steroid and lipid metabolism. Thus, Foxa1 and Foxa2, while redundant during development, have evolved divergent roles in the adult liver, ensuring the maintenance of both genes during evolution. Institute for Diabetes, Obesity and Metabolism. Diabetes Research Center (Functional Genomics Core P30-DK19525) 2012-10-01T19:49:44Z 2012-10-01T19:49:44Z 2012-06 2012-01 Article http://purl.org/eprint/type/JournalArticle 1553-7390 1553-7404 http://hdl.handle.net/1721.1/73529 Bochkis, Irina M. et al. “Genome-Wide Location Analysis Reveals Distinct Transcriptional Circuitry by Paralogous Regulators Foxa1 and Foxa2.” Ed. Michael Snyder. PLoS Genetics 8.6 (2012): e1002770. en_US http://dx.doi.org/10.1371/journal.pgen.1002770 PLoS Genetics Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Bochkis, Irina M. Schug, Jonathan Ye, Diana Z. Kurinna, Svitlana Stratton, Sabrina A. Barton, Michelle C. Kaestner, Klaus H. Genome-Wide Location Analysis Reveals Distinct Transcriptional Circuitry by Paralogous Regulators Foxa1 and Foxa2 |
| title | Genome-Wide Location Analysis Reveals Distinct Transcriptional Circuitry by Paralogous Regulators Foxa1 and Foxa2 |
| title_full | Genome-Wide Location Analysis Reveals Distinct Transcriptional Circuitry by Paralogous Regulators Foxa1 and Foxa2 |
| title_fullStr | Genome-Wide Location Analysis Reveals Distinct Transcriptional Circuitry by Paralogous Regulators Foxa1 and Foxa2 |
| title_full_unstemmed | Genome-Wide Location Analysis Reveals Distinct Transcriptional Circuitry by Paralogous Regulators Foxa1 and Foxa2 |
| title_short | Genome-Wide Location Analysis Reveals Distinct Transcriptional Circuitry by Paralogous Regulators Foxa1 and Foxa2 |
| title_sort | genome wide location analysis reveals distinct transcriptional circuitry by paralogous regulators foxa1 and foxa2 |
| url | http://hdl.handle.net/1721.1/73529 |
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