ArticleFrontiers in cell and developmental biology2020
Brahma Related Gene 1 (Brg1) Regulates Cellular Cholesterol Synthesis by Acting as a Co-factor for SREBP2.
Article in Frontiers in cell and developmental biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 39 citations in OpenAlex.
- Prolonged high-dose prenatal caffeine exposure induces organ-specific developmental toxicity: renal p53 downregulation and hepatic caspase-3 upregulation in neonatal mice, supported with in silico studies.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- SWI/SNF Chromatin Remodelling Complex in Hepatic Physiology: Mechanistic Insights Into Development, Homeostasis and Pathogenesis.Journal of cellular and molecular medicine · 2026Review
- Epigenetic Modifications in Alternative Splicing of LDLR pre-mRNA on Hypercholesterolemia Following Aerobic Exercise Training.International journal of molecular sciences · 2025Article
- The chromatin remodeling protein BRG1 regulates HSC-myofibroblast differentiation and liver fibrosis.Cell death & disease · 2023Article
- Targetable Brg1-CXCL14 axis contributes to alcoholic liver injury by driving neutrophil trafficking.EMBO molecular medicine · 2023Article
- Stress mechanism involved in the progression of alcoholic liver disease and the therapeutic efficacy of nanoparticles.Frontiers in immunology · 2023Review
- Regulation of cholesterol homeostasis in health and diseases: from mechanisms to targeted therapeutics.Signal transduction and targeted therapy · 2022Review
- Trans-activation of eotaxin-1 by Brg1 contributes to liver regeneration.Cell death & disease · 2022Article
- Lysine demethylase 3A is a positive regulator of cardiac myofibroblast transdifferentiation that increases Smad3 phosphorylation following transforming growth factor beta1 stimulation.Molecular biology reports · 2022Article
- Lipid Metabolism and Epigenetics Crosstalk in Prostate Cancer.Nutrients · 2022Review
- Intracellular Cholesterol Synthesis and Transport.Frontiers in cell and developmental biology · 2022Review
- HES5-mediated repression of LIGHT transcription may contribute to apoptosis in hepatocytes.Cell death discovery · 2021Article
- Redox-sensitive activation of CCL7 by BRG1 in hepatocytes during liver injury.Redox biology · 2021Article
- Prostate Cancer-Focus on Cholesterol.Cancers · 2021Review
- DDIT4 S-Nitrosylation Aids p38-MAPK Signaling Complex Assembly to Promote Hepatic Reactive Oxygen Species Production.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Dual Regulation of Tank Binding Kinase 1 by BRG1 in Hepatocytes Contributes to Reactive Oxygen Species Production.Frontiers in cell and developmental biology · 2021Article
- An E2F5-TFDP1-BRG1 Complex Mediates Transcriptional Activation of MYCN in Hepatocytes.Frontiers in cell and developmental biology · 2021Article
- TFCP2 Overcomes Senescence by Cooperating With SREBP2 to Activate Cholesterol Synthesis in Pancreatic Cancer.Frontiers in oncology · 2021Article
- Down-Regulation of CXXC5 De-Represses MYCL1 to Promote Hepatic Stellate Cell Activation.Frontiers in cell and developmental biology · 2021Article
- The Chromatin Remodeling Protein BRG1 Regulates SREBP Maturation by Activating SCAP Transcription in Hepatocytes.Frontiers in cell and developmental biology · 2021Article
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocyte is a hub for cholesterol metabolism. Augmented synthesis of cholesterol in the liver is associated with hypercholesterolemia and contributes to the pathogenesis of a host of cardiovascular and metabolic diseases. Sterol response element binding protein 2 (SREBP2) regulates hepatic cholesterol metabolism by activating the transcription of rate-limiting enzymes in the cholesterol biosynthesis pathway. The underlying epigenetic mechanism is not well understood. We report here that mice with hepatocyte-specific knockout (CKO) of Brg1, a chromatin remodeling protein, exhibit reduced levels of hepatic cholesterol compared to the wild type (WT) littermates when placed on a high-fact diet (HFD) or a methionine-and-choline-deficient diet (MCD). Down-regulation of cholesterol levels as a result of BRG1 deficiency was accompanied by attenuation of cholesterogenic gene transcription. Likewise, BRG1 knockdown in hepatocytes markedly suppressed the induction of cholesterogenic genes by lipid depletion formulas. Brg1 interacted with SREBP2 and was recruited by SREBP2 to the cholesterogenic gene promoters. Reciprocally, Brg1 deficiency dampened the occupancies of SREBP2 on target promoters likely through modulating H3K9 methylation on the cholesterogenic gene promoters. Mechanistically, Brg1 recruited the H3K9 methyltransferase KDM3A to co-regulate pro-cholesterogenic transcription. KDM3A silencing dampened the cholesterogenic response in hepatocytes equivalent to Brg1 deficiency. In conclusion, our data demonstrate a novel epigenetic pathway that contributes to SREBP2-dependent cholesterol synthesis in hepatocytes.
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