E2F-mediated growth regulation requires transcription factor cooperation

Paul R. Van Ginkel, Kuang Ming Hsiao, Hilde Schjerven, Peggy J. Farnham

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57 Scopus citations

Abstract

Previous studies have indicated that the presence of an E2F site is not sufficient for G1/S phase transcriptional regulation. For example, the E2F sites in the E2F1 promoter are necessary, but not sufficient, to mediate differential promoter activity in G0 and S phase. We have now utilized the E2F1 minimal promoter to test several hypotheses that could account for these observations. To test the hypothesis that G1/S phase regulation is achieved via E2F-mediated repression of a strong promoter, a variety of transactivation domains were brought to the E2F1 minimal promoter. Although many of these factors caused increased promoter activity, growth regulation was not observed, suggesting that a general repression model is incorrect. However, constructs having CCAAT or YY1 sites or certain GC boxes cloned upstream of the E2F1 minimal promoter displayed E2F site-dependent regulation. Further analysis of the promoter activity suggested that E2F requires cooperation with another factor to activate transcription in S phase. However, we found that the requirement for E2F to cooperate with additional factors to achieve growth regulation could be relieved by bringing the E2F1 activation domain to the promoter via a Ga14 DNA binding domain. Our results suggest a model that explains why some, but not all, promoters that contain E2F sites display growth regulation.

Original languageEnglish (US)
Pages (from-to)18367-18374
Number of pages8
JournalJournal of Biological Chemistry
Volume272
Issue number29
DOIs
StatePublished - Jul 18 1997
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry

Cite this

Van Ginkel, P. R., Hsiao, K. M., Schjerven, H., & Farnham, P. J. (1997). E2F-mediated growth regulation requires transcription factor cooperation. Journal of Biological Chemistry, 272(29), 18367-18374. https://doi.org/10.1074/jbc.272.29.18367