Changes in nucleosome occupancy associated with metabolic alterations in aged mammalian liver.
Cell Rep
; 9(3): 996-1006, 2014 Nov 06.
Article
em En
| MEDLINE
| ID: mdl-25437555
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Envelhecimento
/
Nucleossomos
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Fígado
/
Mamíferos
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2014
Tipo de documento:
Article
País de publicação:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
/
UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA