Changes in Nucleosome Occupancy Associated with Metabolic Alterations in Aged Mammalian Liver
Aging is accompanied by physiological impairments, which, in insulin-responsive tissues, including the liver, predispose individuals to metabolic disease. However, the molecular mechanisms underlying these changes remain largely unknown. Here, we analyze genome-wide profiles of RNA and chromatin org...
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| Format: | Article |
| Language: | en_US |
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Elsevier B.V.
2015
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| Online Access: | http://hdl.handle.net/1721.1/96715 https://orcid.org/0000-0001-8567-2049 https://orcid.org/0000-0002-6664-2597 |
| _version_ | 1811096531544047616 |
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| author | Bochkis, Irina M. Przybylski, Dariusz Chen, Jennifer Regev, Aviv |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Bochkis, Irina M. Przybylski, Dariusz Chen, Jennifer Regev, Aviv |
| author_sort | Bochkis, Irina M. |
| collection | MIT |
| description | Aging is accompanied by physiological impairments, which, in insulin-responsive tissues, including the liver, predispose individuals to metabolic disease. However, the molecular mechanisms underlying these changes remain largely unknown. Here, we analyze genome-wide profiles of RNA and chromatin organization in the liver of young (3 months) and old (21 months) mice. Transcriptional changes suggest that derepression of the nuclear receptors PPARα, PPARγ, and LXRα in aged mouse liver leads to activation of targets regulating lipid synthesis and storage, whereas age-dependent changes in nucleosome occupancy are associated with binding sites for both known regulators (forkhead factors and nuclear receptors) and candidates associated with nuclear lamina (Hdac3 and Srf) implicated to govern metabolic function of aging liver. Winged-helix transcription factor Foxa2 and nuclear receptor corepressor Hdac3 exhibit a reciprocal binding pattern at PPARα targets contributing to gene expression changes that lead to steatosis in aged liver. |
| first_indexed | 2024-09-23T16:45:10Z |
| format | Article |
| id | mit-1721.1/96715 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:45:10Z |
| publishDate | 2015 |
| publisher | Elsevier B.V. |
| record_format | dspace |
| spelling | mit-1721.1/967152022-10-03T08:01:58Z Changes in Nucleosome Occupancy Associated with Metabolic Alterations in Aged Mammalian Liver Bochkis, Irina M. Przybylski, Dariusz Chen, Jennifer Regev, Aviv Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Biology Chen, Jennifer Regev, Aviv Aging is accompanied by physiological impairments, which, in insulin-responsive tissues, including the liver, predispose individuals to metabolic disease. However, the molecular mechanisms underlying these changes remain largely unknown. Here, we analyze genome-wide profiles of RNA and chromatin organization in the liver of young (3 months) and old (21 months) mice. Transcriptional changes suggest that derepression of the nuclear receptors PPARα, PPARγ, and LXRα in aged mouse liver leads to activation of targets regulating lipid synthesis and storage, whereas age-dependent changes in nucleosome occupancy are associated with binding sites for both known regulators (forkhead factors and nuclear receptors) and candidates associated with nuclear lamina (Hdac3 and Srf) implicated to govern metabolic function of aging liver. Winged-helix transcription factor Foxa2 and nuclear receptor corepressor Hdac3 exhibit a reciprocal binding pattern at PPARα targets contributing to gene expression changes that lead to steatosis in aged liver. National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (K01 award DK-101633) National Human Genome Research Institute (U.S.) (NHGRI CEGS P50 HG006193) Howard Hughes Medical Institute 2015-04-22T19:07:16Z 2015-04-22T19:07:16Z 2014-11 2014-08 Article http://purl.org/eprint/type/JournalArticle 22111247 http://hdl.handle.net/1721.1/96715 Bochkis, Irina M., Dariusz Przybylski, Jenny Chen, and Aviv Regev. “Changes in Nucleosome Occupancy Associated with Metabolic Alterations in Aged Mammalian Liver.” Cell Reports 9, no. 3 (November 2014): 996–1006. https://orcid.org/0000-0001-8567-2049 https://orcid.org/0000-0002-6664-2597 en_US http://dx.doi.org/10.1016/j.celrep.2014.09.048 Cell Reports Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License http://creativecommons.org/licenses/by-nc-nd/3.0/ application/pdf Elsevier B.V. Elsevier Open Access |
| spellingShingle | Bochkis, Irina M. Przybylski, Dariusz Chen, Jennifer Regev, Aviv Changes in Nucleosome Occupancy Associated with Metabolic Alterations in Aged Mammalian Liver |
| title | Changes in Nucleosome Occupancy Associated with Metabolic Alterations in Aged Mammalian Liver |
| title_full | Changes in Nucleosome Occupancy Associated with Metabolic Alterations in Aged Mammalian Liver |
| title_fullStr | Changes in Nucleosome Occupancy Associated with Metabolic Alterations in Aged Mammalian Liver |
| title_full_unstemmed | Changes in Nucleosome Occupancy Associated with Metabolic Alterations in Aged Mammalian Liver |
| title_short | Changes in Nucleosome Occupancy Associated with Metabolic Alterations in Aged Mammalian Liver |
| title_sort | changes in nucleosome occupancy associated with metabolic alterations in aged mammalian liver |
| url | http://hdl.handle.net/1721.1/96715 https://orcid.org/0000-0001-8567-2049 https://orcid.org/0000-0002-6664-2597 |
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