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Nucleic Acids Res. 1997 September 15; 25(18): 3621–3628.
PMCID: PMC146931

The transcriptional activation and repression domains of RFX1, a context-dependent regulator, can mutually neutralize their activities.

Abstract

EP is a DNA element found in regulatory regions of viral and cellular genes. While being a key functional element in viral enhancers, EP has no intrinsic enhancer activity but can stimulate or silence transcription in a context-dependent manner. The EP element is bound by RFX1, which belongs to a novel, evolutionarily conserved protein family. In an attempt to decipher the mechanism by which EP regulates transcription, the intrinsic transcriptional activity of RFX1 was investigated. A functional dissection of RFX1, by analysis of deletion mutants and chimeric proteins, identified several regions with independent transcriptional activity. An activation domain containing a glutamine-rich region is found in the N-terminal half of RFX1, while a region with repressor activity overlaps the C-terminal dimerization domain. In RFX1 these activities were mutually neutralized, producing a nearly inactive transcription factor. This neutralization effect was reproduced by fusing RFX1 sequences to a heterologous DNA-binding domain. We propose that relief of self-neutralization may allow RFX1 to act as a dual-function regulator via its activation and repression domains, accounting for the context-dependent activity of EP.

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Selected References

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