ArticleProceedings of the National Academy of Sciences of the United States of America2000
Sterol regulation of human fatty acid synthase promoter I requires nuclear factor-Y- and Sp-1-binding sites.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 83 citations in OpenAlex.
- PMVK drives hepatocarcinogenesis via SP1 phosphorylation-mediated lipid metabolic reprogramming.Science advances · 2026Article
- COL1A1 proximal promoter topology regulates its transcriptional response to transforming growth factor β.Connective tissue research · 2024Article
- Transcription factor NFYa controls cardiomyocyte metabolism and proliferation during mouse fetal heart development.Developmental cell · 2023Article
- Protective effect of miR-33-5p on the M1/M2 polarization of microglia and the underlying mechanism.Bioengineered · 2022Article
- Review
- The Metabolic Mechanisms of Breast Cancer Metastasis.Frontiers in oncology · 2020Review
- Effects of Genetic Variants of Nuclear Receptor Y on the Risk of Type 2 Diabetes Mellitus.Journal of diabetes research · 2019Article
- SREBP-regulated lipid metabolism: convergent physiology - divergent pathophysiology.Nature reviews. Endocrinology · 2017Review
- NF-Y (CBF) regulation in specific cell types and mouse models.Biochimica et biophysica acta. Gene regulatory mechanisms · 2017Review
- Branched-chain amino acids prevent hepatic fibrosis and development of hepatocellular carcinoma in a non-alcoholic steatohepatitis mouse model.Oncotarget · 2017Article
- Targeting metabolism in breast cancer: How far we can go?World journal of clinical oncology · 2016Review
- NF-Y activates genes of metabolic pathways altered in cancer cells.Oncotarget · 2016Article
- Regulation of the cholesterol biosynthetic pathway and its integration with fatty acid biosynthesis in the oleaginous microalga Nannochloropsis oceanica.Biotechnology for biofuels · 2014Article
- Fatty acid synthase and liver triglyceride metabolism: housekeeper or messenger?Biochimica et biophysica acta · 2012Review
- Sp1 transcription factor interaction with accumulated prelamin a impairs adipose lineage differentiation in human mesenchymal stem cells: essential role of sp1 in the integrity of lipid vesicles.Stem cells translational medicine · 2012Article
- Role of sp transcription factors in the regulation of cancer cell metabolism.Genes & cancer · 2011Article
- Review
- Article
- Sterol-independent repression of low density lipoprotein receptor promoter by peroxisome proliferator activated receptor gamma coactivator-1alpha (PGC-1alpha).Experimental & molecular medicine · 2009Article
- Parasympathetic response in chick myocytes and mouse heart is controlled by SREBP.The Journal of clinical investigation · 2008Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
To understand cholesterol-mediated regulation of human fatty acid synthase promoter I, we tested various 5'-deletion constructs of promoter I-luciferase reporter gene constructs in HepG2 cells. The reporter gene constructs that contained only the Sp-1-binding site (nucleotides -82 to -74) and the two tandem sterol regulatory elements (SREs; nucleotides -63 to -46) did not respond to cholesterol. Only the reporter gene constructs containing a nuclear factor-Y (NF-Y) sequence, the CCAAT sequence (nucleotides -90 to -86), an Sp-1 sequence, and the two tandem SREs responded to cholesterol. The NF-Y-binding site, therefore, is essential for cholesterol response. Mutating the SREs or the NF-Y site and inserting 4 bp between the Sp-1- and NF-Y-binding sites both resulted in a minimal cholesterol response of the reporter genes. Electrophoretic mobility-shift assays using anti-SRE-binding protein (SREBP) and anti-NF-Ya antibodies confirmed that these SREs and the NF-Y site bind the respective factors. We also identified a second Sp-1 site located between nucleotides -40 and -30 that can substitute for the mutated Sp-1 site located between nucleotides -82 and -74. The reporter gene expression of the wild-type promoter and the Sp-1 site (nucleotides -82 to -74) mutant promoter was similar when SREBP1a [the N-terminal domain of SREBP (amino acids 1-520)] was constitutively overexpressed, suggesting that Sp-1 recruits SREBP to the SREs. Under the same conditions, an NF-Y site mutation resulted in significant loss of reporter gene expression, suggesting that NF-Y is required to activate the cholesterol response.
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Registered trials
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.