Nutrient regulation of gene expression by the sterol regulatory element binding proteins: Increased recruitment of gene-specific coregulatory factors and selective hyperacetylation of histone H3 in vivo
- 6 June 2000
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 97 (12) , 6340-6344
- https://doi.org/10.1073/pnas.97.12.6340
Abstract
We have evaluated the mechanism for sterol-regulated gene expression by the sterol regulatory element binding proteins (SREBPs) in intact cells. We show that activation of SREBPs by sterol depletion results in the increased binding of Sp1 to a site adjacent to SREBP in the promoter for the low density lipoprotein (LDL) receptor gene in vivo. Similarly, sterol depletion resulted in the increased recruitment of two distinct SREBP coregulatory factors, NF-Y and CREB, to the promoter for hydroxymethyl glutaryl CoA reductase, another key gene of intracellular cholesterol homeostasis. Furthermore, increased acetylation of histone H3 but not H4 was also detected in chromatin from both promoters on SREBP activation. Thus, SREBP activation results in the similar selective recruitment of different coregulatory generic transcription factors to two separate cholesterol-regulated promoters. These studies demonstrate the utility of the chromatin immunoprecipitation technique for analyzing the differential action of low-abundance transcription factors in fundamental regulatory events in intact cells. Our results also provide key in vivo support for the mechanism proposed from cell-free experiments, where SREBP increased the binding of Sp1 to the LDL receptor promoter. Finally, our findings also indicate that subtle differences in the pattern of core histone acetylation play a role in selective gene activation.Keywords
This publication has 28 references indexed in Scilit:
- Virus Infection Leads to Localized Hyperacetylation of Histones H3 and H4 at the IFN-β PromoterMolecular Cell, 1999
- Transcription Factor-Specific Requirements for Coactivators and Their Acetyltransferase FunctionsScience, 1998
- The Transcriptional Coactivators p300 and CBP Are Histone AcetyltransferasesPublished by Elsevier ,1996
- SREBP transcriptional activity is mediated through an interaction with the CREB-binding protein.Genes & Development, 1996
- A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1ANature, 1996
- A Direct Role for Sterol Regulatory Element Binding Protein in Activation of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase GeneJournal of Biological Chemistry, 1996
- Domains of transcription factor Sp1 required for synergistic activation with sterol regulatory element binding protein 1 of low density lipoprotein receptor promoter.Proceedings of the National Academy of Sciences, 1995
- Cooperation by Sterol Regulatory Element-binding Protein and Sp1 in Sterol Regulation of Low Density Lipoprotein Receptor GeneJournal of Biological Chemistry, 1995
- SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysisCell, 1994
- [19] Receptor-mediated endocytosis of low-density lipoprotein in cultured cellsPublished by Elsevier ,1983