Cited by 78Genomics and Chromatin DynamicsPeroxisome Proliferator-Activated ReceptorsGenetics, Aging, and Longevity in Model Organisms

Changes in nucleosome occupancy associated with metabolic alterations in aged mammalian liver

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Bochkis, Irina M., Przybylski, Dariusz, Chen, Jenny, Regev, Aviv·2014·Cell Reports

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.

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Crossref · 10.1016/j.celrep.2014.09.048

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  • Nucleosome occupancy changes are associated with global upregulation of gene expression with age in yeast and increased FOXA2 binding in aged mammalian livers.

    “Interestingly, nucleosome occupancy changes have also been demonstrated to be associated with the global upregulation of gene expression with age in yeast (Hu et al., 2014) and increased transcription factor (FOXA2) binding in aged mammalian livers (Bochkis et al., 2014).”

    From The Aging Epigenome (2016) · cites this paper as Bochkis et al., 2014

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  1. Ding W Gao S Scott RE 2012 Senescence represses the nuclear localization of the serum response factor and differentiation regulates its nuclear localization with lineage specificity 11181183

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Authors
Bochkis, I. M., Przybylski, D., Chen, J., & Regev, A.
Affiliations
Broad Institute (US)
Corresponding author
Bochkis, Irina M.
Venue
Cell Reports
Publisher
Elsevier BV
Published
2014-11
Volume
9
Issue
3
Pages
996-1006
ISSN
2211-1247 (ISSN-L)
OpenAlex
W2020049638
Cited by
78
References
60
Citations by year
2026: 4 · 2025: 3 · 2024: 6 · 2023: 7 · 2022: 6 · 2021: 10 · 2020: 10 · 2019: 9 · 2018: 8 · 2017: 9 · 2016: 4 · 2015: 2
FWCI
2.05
Type
journal article
Language
en
Open access
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
Funders
  • Howard Hughes Medical Institute
  • National Human Genome Research Institute (P50HG006193, T32HG002295)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK-101633, K01DK101633)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords
aging, liver, nucleosome occupancy, chromatin organization, nuclear receptors, PPARα, PPARγ, liver X receptor alpha, lipid metabolism, steatosis, forkhead transcription factor, nuclear lamina, HDAC3, SRF, FOXA2, transcriptional derepression, insulin resistance, metabolic disorders
MeSH terms
Histone Deacetylase 3, Aging, Animals, Base Sequence, DNA-Binding Proteins, Fatty Liver, Histone Deacetylases, Inflammation, Liver, Male, Mammals, Mice, Inbred C57BL, Models, Biological, Molecular Sequence Data, Nucleosomes, Protein Binding, Transcription Factors, Gene Expression Regulation, Developmental, Nuclear Lamina, PPAR alpha, Hepatocyte Nuclear Factor 3-beta

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