Identification of a functional hepatocyte nuclear factor 4 binding site in the neutral ceramidase promoter
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Identification of a functional hepatocyte nuclear factor 4 binding site in the neutral ceramidase promoter. / Maltesen, Henrik R; Troelsen, Jesper T; Olsen, Jørgen.
I: Journal of Cellular Biochemistry, Bind 111, Nr. 5, 01.12.2010, s. 1330-6.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Identification of a functional hepatocyte nuclear factor 4 binding site in the neutral ceramidase promoter
AU - Maltesen, Henrik R
AU - Troelsen, Jesper T
AU - Olsen, Jørgen
N1 - Copyright © 2010 Wiley-Liss, Inc.
PY - 2010/12/1
Y1 - 2010/12/1
N2 - 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-4a 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-4a binding site predicted by bioinformatic analysis to be present in the Asah2 promoter. Using supershift analysis, HNF-4a overexpression, and HNF-4a knockdown experiments it was confirmed that the predicted HNF-4a binding site identified in the Asah2 promoter is functional. The results support the hypothesis that HNF-4a might be important for intestinal glycolipid metabolism.
AB - 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-4a 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-4a binding site predicted by bioinformatic analysis to be present in the Asah2 promoter. Using supershift analysis, HNF-4a overexpression, and HNF-4a knockdown experiments it was confirmed that the predicted HNF-4a binding site identified in the Asah2 promoter is functional. The results support the hypothesis that HNF-4a might be important for intestinal glycolipid metabolism.
KW - Animals
KW - Binding Sites
KW - Gene Expression Regulation, Enzymologic
KW - Glycolipids
KW - Hepatocyte Nuclear Factor 4
KW - Intestine, Small
KW - Mice
KW - Mice, Inbred C57BL
KW - Microvilli
KW - Neutral Ceramidase
KW - Promoter Regions, Genetic
KW - RNA, Messenger
KW - Tissue Distribution
KW - Transcription Factors
U2 - 10.1002/jcb.22862
DO - 10.1002/jcb.22862
M3 - Journal article
C2 - 20803549
VL - 111
SP - 1330
EP - 1336
JO - Journal of cellular biochemistry. Supplement
JF - Journal of cellular biochemistry. Supplement
SN - 0733-1959
IS - 5
ER -
ID: 33232404