Abstract
BackgroundFive regulatory factor X (RFX) transcription factors (TFs)–RFX1-5–have been previously characterized in the human genome, which have been demonstrated to be critical for development and are associated with an expanding list of serious human disease conditions including major histocompatibility (MHC) class II deficiency and ciliaophathies.ResultsIn this study, we have identified two additional RFX genes–RFX6 and RFX7–in the current human genome sequences. Both RFX6 and RFX7 are demonstrated to be winged-helix TFs and have well conserved RFX DNA binding domains (DBDs), which are also found in winged-helix TFs RFX1-5. Phylogenetic analysis suggests that the RFX family in the human genome has undergone at least three gene duplications in evolution and the seven human RFX genes can be clearly categorized into three subgroups: (1) RFX1-3, (2) RFX4 and RFX6, and (3) RFX5 and RFX7. Our functional genomics analysis suggests that RFX6 and RFX7 have distinct expression profiles. RFX6 is expressed almost exclusively in the pancreatic islets, while RFX7 has high ubiquitous expression in nearly all tissues examined, particularly in various brain tissues.ConclusionThe identification and further characterization of these two novel RFX genes hold promise for gaining critical insight into development and many disease conditions in mammals, potentially leading to identification of disease genes and biomarkers.
Highlights
Five regulatory factor X (RFX) transcription factors (TFs)–RFX1-5–have been previously characterized in the human genome, which have been demonstrated to be critical for development and are associated with an expanding list of serious human disease conditions including major histocompatibility (MHC) class II deficiency and ciliaophathies
In addition to retrieving all known human RFX genes–RFX1-5, we identified two additional genes in the human genome that contain well conserved RFX DNA binding domains (DBDs)
There are no previous publications describing these two genes. We demonstrate that these two genes are RFX gene family members closely related to RFX1-5, and our phylogenetic analysis suggests two separate recent gene duplications leading to the generation of these two genes
Summary
Five regulatory factor X (RFX) transcription factors (TFs)–RFX1-5–have been previously characterized in the human genome, which have been demonstrated to be critical for development and are associated with an expanding list of serious human disease conditions including major histocompatibility (MHC) class II deficiency and ciliaophathies. The X-box motifs, which are typically 14-mer DNA sequences, were initially identified as a result of alignment and inspection of the promoter regions of major histocompatibility complex (MHC) class II genes for conserved DNA elements [2,3]. The first RFX gene (RFX1) was later characterized as a candidate major histocompatibility complex (MHC) class II promoter binding protein [5]. Subsequent studies revealed that RFX1 is not alone Instead, it became the founding member of a novel family of homodimeric and heterodimeric DNA-binding proteins, which includes RFX2 and RFX3 [7]. It became the founding member of a novel family of homodimeric and heterodimeric DNA-binding proteins, which includes RFX2 and RFX3 [7] More members of this gene family were subsequently identified. A fourth RFX gene (RFX4) was discovered in a human breast tumor tissue [8]
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