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

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.