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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
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Transcriptional activation and repression by Fos are independent functions: the C terminus represses immediate-early

D Gius1, X M Cao, F J Rauscher

  • 1Department of Molecular Genetics and Cell Biology, University of Chicago, Illinois 60637.

Molecular and Cellular Biology
|August 1, 1990
PubMed

Insights

Fos protein can both activate and repress gene transcription. This study identifies a C-terminal domain in Fos responsible for repressing immediate-early genes like Egr-1, distinct from its activation domain.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Transcription Factors

Background:

  • The Fos-Jun complex is known to activate transcription via AP-1 binding sites.
  • Immediate-early genes play crucial roles in cellular responses to stimuli.

Purpose of the Study:

  • To investigate the mechanism by which Fos protein regulates (down-regulates) immediate-early genes.
  • To identify the specific DNA sequences and protein domains involved in Fos-mediated repression.

Main Methods:

  • Analysis of Fos and Jun protein interactions and functional domains.
  • Identification of target DNA sequences for Fos-mediated repression.
  • Mutagenesis studies using Fos and Jun variants.

Main Results:

  • Fos down-regulates immediate-early genes (c-fos, Egr-1, Egr-2) by targeting CArG boxes (CC(A/T)6GG).
  • Repression activity resides in the C-terminal 27 amino acids of c-Fos; Jun does not influence this repression.
  • Fos-related protein Fra-1 also represses Egr-1 expression, suggesting a conserved mechanism.

Conclusions:

  • Fos acts as a dual transcriptional regulator, capable of both activation and repression.
  • Distinct functional domains within Fos mediate its interaction with different regulatory elements (AP-1 sites and CArG boxes).
  • The C-terminal domain of Fos is critical for gene repression, independent of its DNA-binding and Jun-interaction domains.

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