Glucose regulates insulin gene transcription by hyperacetylation of histone H4

Amber Mosley, Sabire Özcan

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Induction of insulin gene expression in response to high blood glucose levels is essential for maintaining glucose homeostasis. Although several transcription factors including Beta-2, Ribe3b1, and Pdx-1 have been shown to play a role in glucose stimulation of insulin gene expression, the exact molecular mechanism(s) by which this regulation occurs is unknown. Previous data demonstrate that the transcription factors Beta-2/NeuroD1 and Pdx-1, which are involved in glucose-stimulated insulin gene expression, interact with the histone acetylase p300, suggesting a role for histone acetylation in glucose regulation of the insulin gene expression. We report that exposure of mouse insulinoma 6 cells to high concentrations of glucose results in hyperacetylation of histone H4 at the insulin gene promoter, which correlates with the increased level of insulin gene transcription. In addition, we demonstrate that hyperacetylation of histone H4 in response to high concentrations of glucose also occurs at the glucose transporter-2 gene promoter. Using histone deacetylase inhibitors, we show that increases in histone H4 acetylation cause stimulation of insulin gene transcription even in the absence of high concentrations of glucose. Furthermore, we show that fibroblasts, which lack insulin gene expression, also lack histone acetylation at the insulin gene promoter. In summary, our data support the idea that high concentrations of glucose stimulate insulin gene expression by causing hyperacetylation of histone H4 at the insulin gene promoter.

Original languageEnglish (US)
Pages (from-to)19660-19666
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number22
DOIs
StatePublished - May 30 2003
Externally publishedYes

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Transcription
Histones
Genes
Insulin
Glucose
Gene expression
Acetylation
Gene Expression
Transcription Factors
Insulinoma
Histone Deacetylase Inhibitors
Facilitative Glucose Transport Proteins
Gene Expression Regulation
Fibroblasts
Blood Glucose
Homeostasis

ASJC Scopus subject areas

  • Biochemistry

Cite this

Glucose regulates insulin gene transcription by hyperacetylation of histone H4. / Mosley, Amber; Özcan, Sabire.

In: Journal of Biological Chemistry, Vol. 278, No. 22, 30.05.2003, p. 19660-19666.

Research output: Contribution to journalArticle

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