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PMID: 2167444 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Minimal subenhancer requirements for high-level polyomavirus DNA replication: a cell-specific synergy of PEA3 and PEA1 sites.

Molecular and cellular biology ·Vol. 10 ·No. 9 ·1990-09-00 ·Pages 4996-5001

Rochford R, Davis CT, Yoshimoto KK, Villarreal LP

Abstract

The cell-specific regulation of DNA replication has important implications for the molecular strategy of cellular gene control. Mouse polyomavirus (Py) DNA replication is examined as a model of cell-specific replication control. Using an FM3A-derived mouse cell line which expresses early viral proteins (FOP cells), we determined the minimal sequence requirements for viral DNA replication. FOP cells were observed to have much simpler enhancer requirements than 3T6 and many other cells and did not need a B enhancer for high levels of DNA replication. Using these cells, we show that the individual or tandem binding sites for several unrelated trans-acting factors which are generally subfunctional as transcriptional enhancers (simian virus 40 A core, TGTGGAATG; EBP20, TGTGGTTTT; PEA1 [an AP-1 analog], GTGACTAA; PEA2, GACCGCAG; and PEA3, AGGAAG) stimulated low levels of Py DNA replication. The ordered dimeric combination of PEA3 and PEA1 factor-binding sites, however, acted synergistically to stimulate viral DNA replication to high wild-type levels. This is in contrast to prior results in which much larger enhancer sequences were necessary for high-level viral DNA replication. PEA3/PEA1-stimulated DNA replication showed a distance and orientation independence relative to the origin, which disagrees with some but not other prior analyses of enhancer-dependent DNA replication. It therefore appears that trans-acting factor-binding sites (enhansons) can generally activate DNA replication and that the AP-1 family of sites may act synergistically with other associated trans-acting factors to strongly affect Py DNA replication in specific cells.

MeSH Terms
Animals Base Sequence Binding Sites Cell Line Core Binding Factor Alpha 1 Subunit DNA Replication DNA-Binding Proteins/metabolism Enhancer Elements, Genetic Genetic Vectors Mice Molecular Sequence Data Polyomavirus/genetics Protein-Tyrosine Kinases/metabolism Proto-Oncogene Proteins c-jun Simian virus 40/genetics Transcription Factor AP-2 Transcription Factors/metabolism
Chemicals
Core Binding Factor Alpha 1 Subunit DNA-Binding Proteins Proto-Oncogene Proteins c-jun Runx2 protein, mouse Transcription Factor AP-2 Transcription Factors Protein-Tyrosine Kinases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Rochford R
Department of Molecular Biology and Biochemistry, University of California, Irvine 92717.
Davis C T
Yoshimoto K K
Villarreal L P
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.10.9.4996-5001.1990
Published
1990-09-00
Pages
4996-5001
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC361134
Subset
IM
Grants
NIGMS NIH HHS · GM 36605 · United States
External Links
PubMed source DOI: 10.1128/mcb.10.9.4996-5001.1990 PMC Full Text View journal details
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