title: 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.
authors.affiliation: Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Katan
authors.forename: R
authors.initials: R
authors.lastname: Agami
authors.forename: Y
authors.initials: Y
authors.lastname: Shaul
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics*; D017353:Gene Deletion; D011993:Recombinant Fusion Proteins / Q000235:genetics; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D004268:DNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors