Regulation of Insulin Gene Transcription by Multiple Histone Acetyltransferases
| Autor: | Megan L. Sampley, Sabire Özcan |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Chromatin Immunoprecipitation
Transcription Genetic Blotting Western Molecular Mechanisms of Disease SAP30 Histones Histone H4 Mice Cell Line Tumor Histone H2A Genetics Animals Insulin p300-CBP Transcription Factors Promoter Regions Genetic Molecular Biology biology Reverse Transcriptase Polymerase Chain Reaction GRB10 Acetylation Cell Biology General Medicine Histone acetyltransferase CREB-Binding Protein HDAC4 Molecular biology enzymes and coenzymes (carbohydrates) Insulin receptor Glucose PCAF biology.protein Insulinoma RNA Interference Protein Binding |
| Zdroj: | DNA and Cell Biology. 31:8-14 |
| ISSN: | 1557-7430 1044-5498 |
| DOI: | 10.1089/dna.2011.1336 |
| Popis: | Glucose-stimulated insulin gene transcription is mainly regulated by a 340-bp promoter region upstream of the transcription start site by beta-cell-enriched transcription factors Pdx-1, MafA, and NeuroD1. Previous studies have shown that histone H4 hyperacetylation is important for acute up-regulation of insulin gene transcription. Until now, only the histone acetyltransferase (HAT) protein p300 has been shown to be involved in this histone H4 acetylation event. In this report we investigated the role of the additional HAT proteins CREB binding protein (CBP), p300/CBP-associated factor (PCAF), and general control of amino-acid synthesis 5 (GCN5) in regulation of glucose-stimulated insulin gene transcription. Utilizing quantitative chromatin immunoprecipitation analysis, we demonstrate that glucose regulates the binding of p300, CBP, PCAF, and GCN5 to the proximal insulin promoter. siRNA-mediated knockdown of each of these HAT proteins revealed that depletion of p300 and CBP leads to a drastic decrease in histone H4 acetylation at the insulin promoter and in insulin gene expression, whereas knockdown of PCAF and GCN5 leads to a more moderate decrease in histone H4 acetylation and insulin gene expression. These data suggest that high glucose mediates the recruitment of p300, CBP, PCAF, and GCN5 to the insulin promoter and that all four HATs are important for insulin gene expression. |
| Databáze: | OpenAIRE |
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