The pancreatic duodenal homeobox-1 protein (Pdx-1) interacts with histone deacetylases Hdac-1 and Hdac-2 on low levels of glucose

Amber Mosley, Sabire Özcan

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

We have previously demonstrated that high concentrations of glucose stimulate insulin gene expression by causing hyperacetylation of histone H4 at the insulin gene promoter. Furthermore, we have shown that the glucose-mediated hyperacetylation of histone H4 depends on the recruitment of the histone acetyltransferase p300 by the beta cell-specific transcription factor Pdx-1. In this study, we demonstrate that the histone deacetylases Hdac-1 and Hdac-2 are rapidly recruited to the insulin promoter in the mouse insulinoma cell line MIN6 when cells are switched from high to low glucose media. Moreover, we demonstrate that the beta cell-specific homeodomain protein Pdx-1 interacts with histone deacetylases Hdac-1 and Hdac-2 at low levels of glucose. In vitro studies indicate that the interaction between Pdx-1 and Hdac-1 or Hdac-2 is direct and requires the C terminus of Pdx-1. Treatment of MIN6 cells with okadaic acid, which inhibits the activity of protein phosphatases, abolishes the interaction of Pdx-1 with Hdac-1 and Hdac-2 on low levels of glucose, suggesting the requirement of a dephosphorylation event for this interaction to occur. These data indicate that insulin gene expression is decreased on low levels of glucose by recruitment of Hdac-1 and Hdac-2 to the insulin promoter by the transcription factor Pdx-1.

Original languageEnglish (US)
Pages (from-to)54241-54247
Number of pages7
JournalJournal of Biological Chemistry
Volume279
Issue number52
DOIs
StatePublished - Dec 24 2004
Externally publishedYes

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Histone Deacetylases
Glucose
Insulin
Gene expression
Histones
Transcription Factors
Homeodomain Proteins
Histone Acetyltransferases
Gene Expression
Okadaic Acid
Insulinoma
Phosphoprotein Phosphatases
pancreatic and duodenal homeobox 1 protein
Genes
Cells
Cell Line

ASJC Scopus subject areas

  • Biochemistry

Cite this

The pancreatic duodenal homeobox-1 protein (Pdx-1) interacts with histone deacetylases Hdac-1 and Hdac-2 on low levels of glucose. / Mosley, Amber; Özcan, Sabire.

In: Journal of Biological Chemistry, Vol. 279, No. 52, 24.12.2004, p. 54241-54247.

Research output: Contribution to journalArticle

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