The RFX1 gene is a member of the regulatory factor X (RFX) gene family, which encodestranscription factors that contain five conserved domains including a highly conserved, centrally located,winged helix DNA binding domain as well as a dimerization domain located in theC-terminal region of the sequence.[8] Apart from the five conserved domains, the RFX proteins diverge significantly. The DNA binding and dimerization domains of the RFX family proteins show no similarities to the other domains with the same functions in other proteins.[6]
The RFX protein family is conserved inS. pombe,S. cerevisiae,C. elegans, mice and humans.[9] There are seven known RFX proteins in humans, five in mice, and one inC. elegans as well as one in each of the two species of yeast.[9][10]
The protein encoded by this gene is structurally related to regulatory factorsX2,X3,X4, andX5. It is a transcriptional activator that can bind DNA as a monomer or as a heterodimer with RFX family members X2, X3, and X5, but not with X4. This protein binds to the Xboxes ofMHC class II genes and is essential for their expression. Also, it can bind to aninverted repeat that is required for expression ofhepatitis B virus genes.[7] The RFX proteins were originally cloned and characterized due to their high affinity for a cis-acting promoter sequence, called the Xbox, found in all MHC class II genes.[6]
Levels of mRNA encoding this protein as well as RFX2 and RFX3 are found to be consistently elevated in thetestis and are variable in other tissues throughout the body.[6]
RFX1 contains a C-terminal sequence with no apparent homology to other RFX proteins. This C-terminal tail contains an acidic region that is thought to aid in crossing the nuclear membrane. Two major functions are hypothesized to this exist for this domain: a contribution to thenuclear localization signal (NLS) as well as the contradictory down-regulation of DNA binding as well as nuclear association. These two functions were originally identified through sequence mutations and translational fusions with gfp (green fluorescent protein) and remain to be confirmed.[11]
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^Pugliatti L, Derre J, Berger R, Ucla C, Reith W, Mach B (Sep 1992). "The genes for MHC class II regulatory factors RFX1 and RFX2 are located on the short arm of chromosome 19".Genomics.13 (4):1307–10.doi:10.1016/0888-7543(92)90052-T.PMID1505960.
Sáfrány G, Perry RP (1993). "Transcription factor RFX1 helps control the promoter of the mouse ribosomal protein-encoding gene rpL30 by binding to its alpha element".Gene.132 (2):279–83.doi:10.1016/0378-1119(93)90208-K.PMID8224874.
Norquay LD, Yang X, Sheppard P, et al. (2003). "RFX1 and NF-1 associate with P sequences of the human growth hormone locus in pituitary chromatin".Mol. Endocrinol.17 (6):1027–38.CiteSeerX10.1.1.325.4046.doi:10.1210/me.2003-0025.PMID12624117.
Maijgren S, Sur I, Nilsson M, Toftgård R (2004). "Involvement of RFX proteins in transcriptional activation from a Ras-responsive enhancer element".Arch. Dermatol. Res.295 (11):482–9.doi:10.1007/s00403-004-0456-5.PMID15024578.S2CID2408607.
