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Cited by 69Histone Deacetylase Inhibitors ResearchLiver Disease Diagnosis and TreatmentLipid metabolism and biosynthesis

An HDAC3-PROX1 corepressor module acts on HNF4α to control hepatic triglycerides

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Armour, Sean M., Remsberg, Jarrett R., Damle, Manashree, Sidoli, Simone, Ho, Wesley Y., Li, Zhenghui, Garcia, Benjamin A., Lazar, Mitchell A.·2017·Nature Communications
DOI 10.1038/s41467-017-00772-5PMC PMC5601916
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Abstract

The histone deacetylase HDAC3 is a critical mediator of hepatic lipid metabolism, and liver-specific deletion of HDAC3 leads to fatty liver. To elucidate the underlying mechanism, here we report a method of cross-linking followed by mass spectrometry to define a high-confidence HDAC3 interactome in vivo that includes the canonical NCoR–HDAC3 complex as well as Prospero-related homeobox 1 protein (PROX1). HDAC3 and PROX1 co-localize extensively on the mouse liver genome, and are co-recruited by hepatocyte nuclear factor 4α (HNF4α). The HDAC3–PROX1 module controls the expression of a gene program regulating lipid homeostasis, and hepatic-specific ablation of either component increases triglyceride content in liver. These findings underscore the importance of specific combinations of transcription factors and coregulators in the fine tuning of organismal metabolism.

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Cited by

Sorted by citations

Authors
Armour, S. M., Remsberg, J. R., Damle, M., Sidoli, S., Ho, W. Y., Li, Z., Garcia, B. A., & Lazar, M. A.
Affiliations
University of Pennsylvania (US)
Corresponding author
Lazar, Mitchell A.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2017-09-15
Volume
8
Issue
1
Pages
549-549
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-017-00772-5
PMC
PMC5601916
OpenAlex
W2754989645
Cited by
69
References
11
Citations by year
2026: 10 · 2025: 4 · 2024: 5 · 2023: 11 · 2022: 5 · 2021: 7 · 2020: 11 · 2019: 10 · 2018: 6
FWCI
3.02
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • University of Pennsylvania (P30 DK050306, P30DK19525)
  • National Cancer Institute (P01CA196539)
  • National Institute of General Medical Sciences (T32GM008275, R01GM110174)
  • National Institute of Diabetes and Digestive and Kidney Diseases (F32DK102284, P30 DK 19525, R37DK043806, R01DK043806, P30DK019525, P30DK050306)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Keywords
HDAC3, Prox1, HNF4α, corepressor complex, hepatic lipid metabolism, hepatic triglycerides, hepatic steatosis, protein-protein interaction, transcriptional regulation, lipid homeostasis, hepatic gene expression
MeSH terms
Prospero-Related Homeobox 1 Protein, Histone Deacetylase 3, Animals, Gene Expression Regulation, Histone Deacetylases, Lipids, Liver, Male, Triglycerides, Mice, Knockout, Homeodomain Proteins, Tumor Suppressor Proteins, Protein Interaction Mapping, Hepatocyte Nuclear Factor 4

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