Changes in Nucleosome Occupancy Associated with Metabolic Alterations in Aged Mammalian Liver
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Regev_Changes in.pdf
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3.09 MB
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Adobe PDF
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Author(s)
Bochkis, Irina M.
Przybylski, Dariusz
Chen, Jennifer
Regev, Aviv
Date Issued
November 2014
Journal
Cell Reports
Publisher
Elsevier B.V.
Citation
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.
Version
Final published version
Abstract
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.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License
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DOI of Published Version
https://doi.org/10.1016/j.celrep.2014.09.048
