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PMID: 7891687 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Binding sites for hepatocyte nuclear factor 3 beta or 3 gamma and pancreas transcription factor 1 are required for efficient expression of the gene encoding pancreatic alpha-amylase.

Molecular and cellular biology ·Vol. 15 ·No. 4 ·1995-04-00 ·Pages 1933-41

Cockell M, Stolarczyk D, Frutiger S, Hughes GJ, Hagenbüchle O, Wellauer PK

Abstract

Efficient expression of genes under the control of alpha-amylase 2 5'-flanking sequences in exocrine pancreatic cells requires, in addition to the pancreas transcription factor 1 binding site (M. Cockell, B.J. Stevenson, M. Strubin, O. Hagenbüchle, and P. K. Wellauer, Mol. Cell. Biol. 9:2464-2476, 1989), another cis-acting element at positions -60 to -86. This DNA element, which contains an AT-rich core, site for nuclear proteins present not only in the pancreas but also in other tissues and cell lines derived from the endoderm. Purification of binding activities from pancreatic cells by DNA affinity chromatography reveals several distinct proteins ranging in size from 45 to 54 kDa (p45, p47/48, and p54). All of these proteins interact with the specific DNA sequence upon renaturation in vitro. Protein sequencing, electrophoretic mobility shift assay, and immunoblot analyses identify p54 and p47/48 as members of the hepatocyte nuclear factor 3 (HNF3 [forkhead]) family of transcription factors. p54 belongs to the subfamily of HNF3 beta proteins, while p47/48 binding activity includes HNF3 gamma. The cDNAs for two HNF3 beta proteins differing only in N-terminal amino acid sequences were isolated from a pancreatic cDNA library. The mRNAs encoding the two protein species accumulate to different steady-state levels in poly(A)+ RNA of pancreatic cells. Our results support a model by which the pancreas-specific expression of the alpha-amylase gene is mediated by a combination of cell-specific and cell lineage-specific transcription factors.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Cells, Cultured DNA-Binding Proteins/genetics,metabolism Gene Expression Regulation Hepatocyte Nuclear Factor 3-beta Hepatocyte Nuclear Factor 3-gamma Molecular Sequence Data Nuclear Proteins/metabolism Pancreas/cytology,enzymology Promoter Regions, Genetic/genetics Protein Binding RNA, Messenger/biosynthesis Rats Sequence Homology, Amino Acid Tissue Distribution Transcription Factors/genetics,metabolism alpha-Amylases/biosynthesis,genetics
Chemicals
DNA-Binding Proteins Foxa2 protein, rat Foxa3 protein, rat Nuclear Proteins RNA, Messenger Transcription Factors XPF-1 protein, human Hepatocyte Nuclear Factor 3-gamma Hepatocyte Nuclear Factor 3-beta alpha-Amylases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Cockell M
Swiss Institute for Experimental Cancer Research, Epalinges/Lausanne.
Stolarczyk D
Frutiger S
Hughes G J
Hagenbüchle O
Wellauer P K
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.15.4.1933
Published
1995-04-00
Pages
1933-41
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC230419
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.15.4.1933 PMC Full Text View journal details
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