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PMID: 9528758 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Rex-1, a gene encoding a transcription factor expressed in the early embryo, is regulated via Oct-3/4 and Oct-6 binding to an octamer site and a novel protein, Rox-1, binding to an adjacent site.

Molecular and cellular biology ·Vol. 18 ·No. 4 ·1998-04-00 ·Pages 1866-78

Ben-Shushan E, Thompson JR, Gudas LJ, Bergman Y

Abstract

The Rex-1 (Zfp-42) gene, which encodes an acidic zinc finger protein, is expressed at high levels in embryonic stem (ES) and F9 teratocarcinoma cells. Prior analysis identified an octamer motif in the Rex-1 promoter which is required for promoter activity in undifferentiated F9 cells and is involved in retinoic acid (RA)-associated reduction in expression. We show here that the Oct-3/4 transcription factor, but not Oct-1, can either activate or repress the Rex-1 promoter, depending on the cellular environment. Rex-1 repression is enhanced by E1A. The protein domain required for Oct-3/4 activation was mapped to amino acids 1 to 35, whereas the domain required for Oct-3/4 repression was mapped to amino acids 61 to 126, suggesting that the molecular mechanisms underlying transcriptional activation and repression differ. Like Oct-3/4, Oct-6 can also lower the expression of the Rex-1 promoter via the octamer site, and the amino-terminal portion of Oct-6 mediates this repression. In addition to the octamer motif, a novel positive regulatory element, located immediately 5' of the octamer motif, was identified in the Rex-1 promoter. Mutations in this element greatly reduce Rex-1 promoter activity in F9 cells. High levels of a binding protein(s), designated Rox-1, recognize this novel DNA element in F9 cells, and this binding activity is reduced following RA treatment. Taken together, these results indicate that the Rex-1 promoter is regulated by specific octamer family members in early embryonic cells and that a novel element also contributes to Rex-1 expression.

MeSH Terms
Animals Binding Sites COS Cells DNA-Binding Proteins/metabolism Gene Expression Regulation, Developmental Octamer Transcription Factor-3 Octamer Transcription Factor-6 Promoter Regions, Genetic Repressor Proteins/metabolism Saccharomyces cerevisiae Proteins Stem Cells/metabolism Transcription Factors/metabolism Transcription, Genetic Tumor Cells, Cultured Zinc Fingers
Chemicals
DNA-Binding Proteins Octamer Transcription Factor-3 ROX1 protein, S cerevisiae Repressor Proteins Saccharomyces cerevisiae Proteins Transcription Factors Octamer Transcription Factor-6
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Ben-Shushan E
Hubert H. Humphrey Center for Experimental Medicine and Cancer Research, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Thompson J R
Gudas L J
Bergman Y
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.18.4.1866
Published
1998-04-00
Pages
1866-78
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC121416
Subset
IM
Grants
NCI NIH HHS · R01CA39036 · United States
External Links
PubMed source DOI: 10.1128/MCB.18.4.1866 PMC Full Text View journal details
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