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Related Experiment Videos

Multiple sequence elements in the c-fos promoter mediate induction by cAMP.

T M Fisch1, R Prywes, M C Simon

  • 1Laboratory of Biochemistry and Molecular Biology, Rockefeller University, New York, New York 10021.

Genes & Development
|February 1, 1989
PubMed
Summary

Cyclic AMP (cAMP) induces c-fos gene expression in NIH-3T3 cells through multiple promoter elements, unlike serum induction which relies on the serum response element (SRE). These cAMP-responsive elements function independently.

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Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Cellular Signaling

Background:

  • The c-fos gene is rapidly induced by various extracellular stimuli.
  • Serum and cyclic AMP (cAMP) are known inducers of c-fos, but their mechanisms may differ.
  • Understanding the cis-regulatory elements governing c-fos induction is crucial for deciphering gene expression control.

Purpose of the Study:

  • To investigate the distinct mechanisms of c-fos induction by cAMP compared to serum.
  • To identify the specific DNA sequence elements in the c-fos promoter/enhancer responsible for cAMP-mediated induction.
  • To determine if these elements can confer cAMP inducibility to a minimal or heterologous promoter.

Main Methods:

  • Utilized NIH-3T3 cells for gene induction studies.

Related Experiment Videos

  • Performed deletion analysis and functional assays of the c-fos promoter/enhancer region.
  • Fused identified c-fos regulatory regions to a cAMP-unresponsive minimal fos promoter and a heterologous promoter to assess their function.
  • Investigated the role of specific transcription factor binding sites, including the serum response element (SRE) and activating transcription factor (ATF) sites.

    • Main Results:

    • cAMP induction of c-fos in NIH-3T3 cells does not require the serum response element (SRE), distinguishing it from serum-induced expression.
    • Multiple distinct sequence elements within the c-fos promoter/enhancer can independently mediate cAMP inducibility.
    • Identified regions including those binding activating transcription factor (ATF) and AP1-homologous sites, as well as the SRE-containing region, as capable of conferring cAMP inducibility.
    • Specific c-fos regions (-700 to -63 and -71 to -48) conferred cAMP inducibility when linked to a heterologous promoter.

    Conclusions:

    • The induction of c-fos by cAMP involves a complex interplay of multiple cis-acting elements within the promoter/enhancer region.
    • These elements function independently and do not rely on a single critical sequence, unlike serum induction.
    • The findings highlight the versatility of the c-fos promoter in responding to different signaling pathways through distinct regulatory elements.