Identification of a functional hepatocyte nuclear factor 4 binding site in the neutral ceramidase promoter

Henrik R. Maltesen, Jesper T. Troelsen, Jørgen Olsen*

*Corresponding author

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

The brush border membrane of the differentiated small intestinal epithelial cell is studded with membrane bound hydrolytic ectoenzymes involved in digestion. Previous studies of the regulation of genes encoding brush border enzymes have especially implicated the transcription factors hepatocyte nuclear factor HNF-1 and Cdx2. Recent genome-wide studies have, however, also identified HNF-4α as a transcription factor with a high number of target genes in the differentiated small intestinal epithelial cell. The Asah2 gene encodes neutral ceramidase, which is a hydrolytic brush border enzyme involved in ceramide digestion. It was the purpose of the present work to experimentally verify the functional importance of a HNF-4α binding site predicted by bioinformatic analysis to be present in the Asah2 promoter. Using supershift analysis, HNF-4α overexpression, and HNF-4α knockdown experiments it was confirmed that the predicted HNF-4α binding site identified in the Asah2 promoter is functional. The results support the hypothesis that HNF-4α might be important for intestinal glycolipid metabolism.

Original languageEnglish
JournalJournal of Cellular Biochemistry
Volume111
Issue number5
Pages (from-to)1330-1336
Number of pages7
ISSN0730-2312
DOIs
Publication statusPublished - 1 Dec 2010
Externally publishedYes

Keywords

  • Asah2
  • HNF-4α
  • intestinal differentiation
  • promoter regulation

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