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Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRα and LXRβ
Open accessAbstract
The liver X receptors (LXRs) are members of the nuclear hormone receptor superfamily that are bound and activated by oxysterols. These receptors serve as sterol sensors to regulate the transcription of gene products that control intracellular cholesterol homeostasis through catabolism and transport. In this report, we describe a novel LXR target, the sterol regulatory element-binding protein-1c gene (SREBP-1c), which encodes a membrane-bound transcription factor of the basic helix-loop-helix-leucine zipper family. SREBP-1c expression was markedly increased in mouse tissues in an LXR-dependent manner by dietary cholesterol and synthetic agonists for both LXR and its heterodimer partner, the retinoid X receptor (RXR). Expression of the related gene products, SREBP-1a and SREBP-2, were not increased. Analysis of the mouse SREBP-1c gene promoter revealed an RXR/LXR DNA-binding site that is essential for this regulation. The transcriptional increase in SREBP-1c mRNA by RXR/LXR was accompanied by a similar increase in the level of the nuclear, active form of the SREBP-1c protein and an increase in fatty acid synthesis. Because this active form of SREBP-1c controls the transcription of genes involved in fatty acid biosynthesis, our results reveal a unique regulatory interplay between cholesterol and fatty acid metabolism.
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Schmelzer, C., Kubo, H., Mori, M., Sawashita, J., Kitano, M., Hosoe, K., Boomgaarden, I., Döring, F., & Higuchi, K. (2010) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.200900155 · Cited by 53
Regulation of fatty acid and cholesterol synthesis: co-operation or competition?
Gibbons, G. F. (2003) · Progress in Lipid Research · doi:10.1016/s0163-7827(03)00034-1 · Cited by 51
Metadata
- Authors
- Repa, J. J., Liang, G., Ou, J., Bashmakov, Y., Lobaccaro, J.-M. A., Shimomura, I., Shan, B., Brown, M. S., Goldstein, J. L., & Mangelsdorf, D. J.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2000-11-15
- Volume
- 14
- Issue
- 22
- Pages
- 2819-2830
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2024851295
- Cited by
- 1,692
- References
- 2
- Type
- posted content
- Language
- en
- Open access
- diamond
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.