c-Myc represses transcription in vivo by a novel mechanism dependent on the initiator element and Myc box II

EMBO J. 1994 Sep 1;13(17):4070-9.

Abstract

We show that c-Myc, in addition to activating transcription through E-box Myc binding sites (Ems), also represses transcription by a mechanism dependent on initiator (Inr) elements of the basal promoters of susceptible genes. Repression was first observed as a component of c-Myc biphasic regulation of the adenovirus-2 major late promoter (MLP), which contains both Inr and Ems sequences. Two differentiation-specific genes containing Inr, the C/EBP alpha and albumin genes, are repressed through their basal promoters by c-Myc, but are activated by the related B-HLH-LZ factor, USF. Repression requires both the B-HLH-LZ and Myc box II (MBII) domains. Significantly, a MBII deletion mutant which is deficient in repression, but transactivates normally, fails to cooperate with an activated ras gene to transform primary fibroblasts. Thus Myc-dependent transactivation is insufficient for Ras cooperation and the novel transcription repression function is implicated in Ras cooperation as well as the suppression of Inr-dependent genes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae / genetics
  • Albumins / genetics
  • Animals
  • Base Sequence
  • CCAAT-Enhancer-Binding Proteins
  • Cell Transformation, Neoplastic / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation*
  • Genes, Reporter
  • Humans
  • Luciferases / biosynthesis
  • Luciferases / genetics
  • Mice
  • Molecular Sequence Data
  • Nuclear Proteins / genetics
  • Promoter Regions, Genetic / genetics*
  • Protein Binding
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Repressor Proteins / metabolism*
  • Structure-Activity Relationship
  • Transcription Factors / metabolism
  • Transcription, Genetic*
  • Upstream Stimulatory Factors

Substances

  • Albumins
  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-myc
  • Repressor Proteins
  • Transcription Factors
  • USF1 protein, human
  • Upstream Stimulatory Factors
  • Usf1 protein, mouse
  • Luciferases