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PMID: 12215259 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

The mouse alpha-fetoprotein promoter is repressed in HepG2 hepatoma cells by hepatocyte nuclear factor-3 (FOXA).

DNA and cell biology ·Vol. 21 ·No. 8 ·2002-08-00 ·Pages 561-9

Huang MC, Li KK, Spear BT

Abstract

The mouse alpha-fetoprotein gene is expressed at high levels in the fetal liver and is transcriptionally silenced at birth. The repression is governed, at least in part, by the 250 base pair (bp) AFP promoter. We show here that the AFP promoter is dramatically repressed by HNF3 in HepG2 hepatoma cells. This repression is governed by the region between -205 and -150. Furthermore, this fragment can confer HNF3-mediated repression on a heterologous promoter. The repression is abolished by a mutation that is centered at -165. EMSA analyses using in vivo and in vitro synthesized proteins indicate that HNF3 proteins do not bind DNA from the -205 to -150 region. We propose that HNF3 represses AFP promoter activity through indirect mechanisms that modulate the binding or activity of a liver-enriched factor that interacts with the -165 region of the AFP promoter.

MeSH Terms
Animals Base Sequence Binding Sites Carcinoma, Hepatocellular DNA-Binding Proteins/physiology Gene Silencing HeLa Cells Hepatocyte Nuclear Factor 3-alpha Hepatocyte Nuclear Factor 3-beta Humans Mice Mutation Nuclear Proteins/physiology Promoter Regions, Genetic Repressor Proteins/physiology Transcription Factors Tumor Cells, Cultured alpha-Fetoproteins/genetics
Chemicals
DNA-Binding Proteins FOXA1 protein, human FOXA2 protein, human Foxa1 protein, mouse Foxa2 protein, mouse Hepatocyte Nuclear Factor 3-alpha Nuclear Proteins Repressor Proteins Transcription Factors alpha-Fetoproteins Hepatocyte Nuclear Factor 3-beta
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Huang Mei-Chuan
Department of Microbiology, University of Kentucky, Lexington, Kentucky 40536-0298, USA.
Li Kelly Ke
Spear Brett T
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Article Info
Journal
DNA and cell biology
Abbr.
DNA Cell Biol
ISSN
1044-5498
DOI
10.1089/104454902320308933
Published
2002-08-00
Pages
561-9
Language
English
Region
United States
NLM ID
9004522
PMCID
PMC1563500
Subset
IM
Grants
NIDDK NIH HHS · DK51600 · United States
NIGMS NIH HHS · GM45253 · United States
External Links
PubMed source DOI: 10.1089/104454902320308933 PMC Full Text View journal details
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