ArticleThe Journal of biological chemistry2016
Histone Deacetylase 1 (HDAC1) Negatively Regulates Thermogenic Program in Brown Adipocytes via Coordinated Regulation of Histone H3 Lysine 27 (H3K27) Deacetylation and Methylation.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 124 citations in OpenAlex.
- Beta 2-adrenergic pathway combats Alzheimer's disease: Restoring cognition and synaptic integrity.Neural regeneration research · 2026Article
- Targeted Strategies of Adipose Stem Cells for Metabolic Diseases: Mechanisms and Clinical Translation Challenges.Stem cell reviews and reports · 2026Review
- Sphingosine kinase 2 regulates adipocyte browning and whole-body metabolism.Science advances · 2026Article
- Photoperiodic modulation of puberty through melatonin-kisspeptin-GnRH signalling in female Wistar rats.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2026Article
- Inhibition of adipocyte RUNX1/2 enhances adipose tissue thermogenesis through distinct mechanisms.Nature communications · 2026Article
- Transient SUMOylation inhibition in human pre-adipocytes stably imprints a transcriptional beiging fate.Nucleic acids research · 2026Article
- Adenylosuccinate Synthase 1 Deficiency Improves Energy Metabolism by Promoting Adipose Tissue Re-esterification via Glycerol Kinase Upregulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Expression profiles of histone H4K20 methylation and its associated enzymes in mouse cardiac disease and human heart failure.Epigenetics · 2025Article
- Epigenetic programming of estrogen receptor in adipocytes by high-fat diet regulates obesity-induced inflammation.JCI insight · 2025Article
- Elevated EBF2 in mouse but not pig drives the progressive brown fat lineage specification via chromatin activation.Journal of advanced research · 2025Article
- Air pollution modulates brown adipose tissue function through epigenetic regulation by HDAC9 and KDM2B.JCI insight · 2025Article
- MS275 Inhibits Neuroblastoma Cell Growth by Mediating H3K27ac/PROX1 Axis In Silico and In Vitro.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Acute chromatin decompaction stiffens the nucleus as revealed by nanopillar-induced nuclear deformation in cells.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- LTA4H improves the tumor microenvironment and prevents HCC progression via targeting the HNRNPA1/LTBP1/TGF-β axis.Cell reports. Medicine · 2025Article
- Butyrate Prevents Obesity Accompanied by HDAC9-Mediated Browning of White Adipose Tissue.Biomedicines · 2025Article
- Maintenance of thermogenic adipose tissues despite loss of the H3K27 acetyltransferases p300 or CBP.American journal of physiology. Endocrinology and metabolism · 2024Article
- Differential regulation of H3K9/H3K14 acetylation by small molecules drives neuron-fate-induction of glioma cell.Cell death & disease · 2023Article
- Management of Obesity and Obesity-Related Disorders: From Stem Cells and Epigenetics to Its Treatment.International journal of molecular sciences · 2023Review
- Roles of Protein Post-Translational Modifications During Adipocyte Senescence.International journal of biological sciences · 2023Review
- Emerging roles of histone deacetylases in adaptive thermogenesis.Frontiers in endocrinology · 2023Review
12 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Inhibiting class I histone deacetylases (HDACs) increases energy expenditure, reduces adiposity, and improves insulin sensitivity in obese mice. However, the precise mechanism is poorly understood. Here, we demonstrate that HDAC1 is a negative regulator of the brown adipocyte thermogenic program. The Hdac1 level is lower in mouse brown fat (BAT) than white fat, is suppressed in mouse BAT during cold exposure or β3-adrenergic stimulation, and is down-regulated during brown adipocyte differentiation. Remarkably, overexpressing Hdac1 profoundly blocks, whereas deleting Hdac1 significantly enhances, β-adrenergic activation-induced BAT-specific gene expression in brown adipocytes. β-Adrenergic activation in brown adipocytes results in a dissociation of HDAC1 from promoters of BAT-specific genes, including uncoupling protein 1 (Ucp1) and peroxisome proliferator-activated receptor γ co-activator 1α (Pgc1α), leading to increased acetylation of histone H3 lysine 27 (H3K27), an epigenetic mark of gene activation. This is followed by dissociation of the polycomb repressive complexes, including the H3K27 methyltransferase enhancer of zeste homologue (EZH2), suppressor of zeste 12 (SUZ12), and ring finger protein 2 (RNF2) from (and concomitant recruitment of H3K27 demethylase ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX) to) Ucp1 and Pgc1α promoters, leading to decreased H3K27 trimethylation, a histone transcriptional repression mark. Thus, HDAC1 negatively regulates the brown adipocyte thermogenic program, and inhibiting Hdac1 promotes BAT-specific gene expression through a coordinated control of increased acetylation and decreased methylation of H3K27, thereby switching the transcriptional repressive state to the active state at the promoters of Ucp1 and Pgc1α. Targeting HDAC1 may be beneficial in prevention and treatment of obesity by enhancing BAT thermogenesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.