PreprintCited by 299Genomics and Chromatin DynamicsEpigenetics and DNA MethylationNuclear Receptors and Signaling

Emerging roles of the corepressors NCoR1 and SMRT in homeostasis

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Mottis, Adrienne, Mouchiroud, Laurent, Auwerx, Johan·2013·Genes & Development

Abstract

Epigenetic regulation of gene expression is strongly influenced by the accessibility of nucleosomal DNA or the state of chromatin compaction. In this context, coregulators, including both coactivators and corepressors, are pivotal intermediates that bridge chromatin-modifying enzymes and transcription factors. NCoR1 (nuclear receptor corepressor) and SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) are among the best-characterized corepressors from a molecular point of view. These coregulators have conserved orthologs in lower organisms, which underscores their functional importance. Here we summarize the results from recent in vivo studies that reveal the wide-ranging roles of NCoR1 and SMRT in developmental as well as homeostatic processes, including metabolism, inflammation, and circadian rhythms. We also discuss the potential implications of NCoR1 and SMRT regulation of pathways ranging from genomic stability and carcinogenesis to metabolic diseases such as type 2 diabetes.

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  • PGC-1α and NCoR1 oppositely regulate several transcription factors, including nuclear respiratory factors, estrogen-related receptors and PPARs.

    “In fact, PGC-1α and NCoR1 oppositely regulate several transcription factors, including nuclear respiratory factors, estrogen-related receptors and PPARs (Scarpulla, 2011; Andreux et al, 2013; Mottis et al, 2013).”

    From Mitochondrial response to nutrient availability and its role in metabolic disease (2014) · cites this paper as Mottis et al, 2013

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Authors
Mottis, A., Mouchiroud, L., & Auwerx, J.
Affiliations
École Polytechnique Fédérale de Lausanne (CH)
Venue
Genes & Development
Published
2013-04-15
Volume
27
Issue
8
Pages
819-835
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
OpenAlex
W2139472488
Cited by
297
References
117
Citations by year
2026: 11 · 2025: 16 · 2024: 18 · 2023: 29 · 2022: 34 · 2021: 34 · 2020: 29 · 2019: 28 · 2018: 17 · 2017: 22 · 2016: 18 · 2015: 19 · 2014: 17 · 2013: 4
Type
posted content
Language
en
Open access
Licence
other-oa
Locations
  • Genes & Development (publishedVersion, other-oa)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
Funders
  • National Science Foundation (310030)
  • Velux Stiftung
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (136201, 31003A, 143748, 124713, 310030)
  • National Institutes of Health
  • National Institute on Aging (R01AG043930)
  • National Heart, Lung, and Blood Institute (R01HL106511-01A, R01HL106511)
  • FP7 Ideas: European Research Council (231138)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
NCOR1, SMRT, nuclear receptor corepressor, corepressors, epigenetic regulation, chromatin condensation, transcriptional co-regulation, homeostasis, metabolism, inflammation, circadian rhythm, genome stability, carcinogenesis, type 2 diabetes
MeSH terms
Animals, Gene Expression Regulation, Homeostasis, Humans, Nuclear Receptor Co-Repressor 1, Nuclear Receptor Co-Repressor 2

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