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Identification and characterization of novel human tissue-specific RFX transcription factors.

Aftab S, Semenec L, Chu JS, Chen N - BMC Evol. Biol. (2008)

Bottom Line: 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.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.The 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC, V5A 1S6, Canada. saaftab@sfu.ca

ABSTRACT

Background: 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.

Results: In 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.

Conclusion: The 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.

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Functional domains in the known and novel human RFX genes. The functional domains, AD, DBD, B, C, and D are indicated using color-coded boxes. Genes are represented using horizontal lines, which are proportional to the protein lengths. The domain lengths and positions are also proportional to their actual lengths. The graphs are aligned based on the position of the DBDs.
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Figure 2: Functional domains in the known and novel human RFX genes. The functional domains, AD, DBD, B, C, and D are indicated using color-coded boxes. Genes are represented using horizontal lines, which are proportional to the protein lengths. The domain lengths and positions are also proportional to their actual lengths. The graphs are aligned based on the position of the DBDs.

Mentions: In addition to the highly conserved DBDs, other domains including ADs, B, C, and D domains (also known as dimerization domain) [13] have been described in human RFX1-3 (Figure 2). Among these functional domains, ADs have been identified in RFX1-3. However, ADs have not been identified RFX4-5. The B and C domains, which are usually called extended dimerization domains, play supporting roles in dimerization [16]. B, C, and D domains have also been identified in RFX4 but are missing from RFX5. Using InterProScan [32] and HMMER [29], we have found that RFX6 possesses B, C, and D domains, but not AD (Figure 2). The motif composition of RFX6 is similar to RFX4, which also has B, C, and D domains but lacks AD. In contrast, we failed to identify B, C, and D domains or AD in RFX7. None of these domains can be found in RFX5 as well. Because these C-terminal domains–B, C, and D domains–have been shown to mediate dimerization as well as transcriptional repression [33], RFX6, which contains B, C, D domain, and RFX7, which does not possess B, C, or D domains, may therefore play different role in transcriptional regulation.


Identification and characterization of novel human tissue-specific RFX transcription factors.

Aftab S, Semenec L, Chu JS, Chen N - BMC Evol. Biol. (2008)

Functional domains in the known and novel human RFX genes. The functional domains, AD, DBD, B, C, and D are indicated using color-coded boxes. Genes are represented using horizontal lines, which are proportional to the protein lengths. The domain lengths and positions are also proportional to their actual lengths. The graphs are aligned based on the position of the DBDs.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2533330&req=5

Figure 2: Functional domains in the known and novel human RFX genes. The functional domains, AD, DBD, B, C, and D are indicated using color-coded boxes. Genes are represented using horizontal lines, which are proportional to the protein lengths. The domain lengths and positions are also proportional to their actual lengths. The graphs are aligned based on the position of the DBDs.
Mentions: In addition to the highly conserved DBDs, other domains including ADs, B, C, and D domains (also known as dimerization domain) [13] have been described in human RFX1-3 (Figure 2). Among these functional domains, ADs have been identified in RFX1-3. However, ADs have not been identified RFX4-5. The B and C domains, which are usually called extended dimerization domains, play supporting roles in dimerization [16]. B, C, and D domains have also been identified in RFX4 but are missing from RFX5. Using InterProScan [32] and HMMER [29], we have found that RFX6 possesses B, C, and D domains, but not AD (Figure 2). The motif composition of RFX6 is similar to RFX4, which also has B, C, and D domains but lacks AD. In contrast, we failed to identify B, C, and D domains or AD in RFX7. None of these domains can be found in RFX5 as well. Because these C-terminal domains–B, C, and D domains–have been shown to mediate dimerization as well as transcriptional repression [33], RFX6, which contains B, C, D domain, and RFX7, which does not possess B, C, or D domains, may therefore play different role in transcriptional regulation.

Bottom Line: 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.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.The 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC, V5A 1S6, Canada. saaftab@sfu.ca

ABSTRACT

Background: 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.

Results: In 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.

Conclusion: The 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.

Show MeSH