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. 1994 Sep 1;13(17):4070–4079. doi: 10.1002/j.1460-2075.1994.tb06724.x

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

L H Li 1, C Nerlov 1, G Prendergast 1, D MacGregor 1, E B Ziff 1
PMCID: PMC395328  PMID: 8076602

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.

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Selected References

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