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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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Relative expression of human RFX genes revealed by SAGE. Original SAGE libraries were generated by the Mouse Atlas Project [37]. X-axis shows different tissue types, while Y-axis shows relative SAGE tag frequency.
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Figure 5: Relative expression of human RFX genes revealed by SAGE. Original SAGE libraries were generated by the Mouse Atlas Project [37]. X-axis shows different tissue types, while Y-axis shows relative SAGE tag frequency.

Mentions: Second, to gain a quantitative understanding of the expression of RFX genes, we took advantage of the recent availability of serial analysis of gene expression (SAGE) libraries constructed by the Mouse Atlas of Gene Expression Project http://www.mouseatlas.org/[37]. To start with, we tested the hypothesis that the expression of mouse RFX TFs approximates the expression of human RFX TFs. We analyzed 196 mouse SAGE libraries, each of which was produced by using a RNA library prepared from different tissue types (some of which are duplicates). Different SAGE libraries contain slightly different number of total SAGE tags. To ensure that SAGE tags and tag counts were comparable between different SAGE libraries all the libraries were normalized to 1,000,000 SAGE tags. Qualitatively, expression profiles of mouse RFX genes obtained from SAGE analysis are consistent with the expression profiles of human RFX genes obtained from the dbEST database analysis, as well as previous publications about human RFX gene expressions (Figure 5). In contrast to all other RFX genes–RFX1-5 and RFX7, which are heavily expressed in the brain, RFX6 is clearly absent from all types of brain tissues (Figure 5). RFX6 is primarily found in the pancreas (Figure 5) which is consistent with results obtained from analyzing dbEST. Low level expression of RFX6 is found in liver (also detected in dbEST) and heart. In addition to the high tissue-specificity, RFX6 has the lowest overall expression level among all seven RFX genes, suggesting that RFX6 may be under tighter regulatory control. In contrast, RFX7 has the highest relative expression level among all seven mouse RFX genes. Similar to RFX1 and RFX5, RFX7 is found in essentially all types of tissues that were examined (Figure 5).


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

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

Relative expression of human RFX genes revealed by SAGE. Original SAGE libraries were generated by the Mouse Atlas Project [37]. X-axis shows different tissue types, while Y-axis shows relative SAGE tag frequency.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Relative expression of human RFX genes revealed by SAGE. Original SAGE libraries were generated by the Mouse Atlas Project [37]. X-axis shows different tissue types, while Y-axis shows relative SAGE tag frequency.
Mentions: Second, to gain a quantitative understanding of the expression of RFX genes, we took advantage of the recent availability of serial analysis of gene expression (SAGE) libraries constructed by the Mouse Atlas of Gene Expression Project http://www.mouseatlas.org/[37]. To start with, we tested the hypothesis that the expression of mouse RFX TFs approximates the expression of human RFX TFs. We analyzed 196 mouse SAGE libraries, each of which was produced by using a RNA library prepared from different tissue types (some of which are duplicates). Different SAGE libraries contain slightly different number of total SAGE tags. To ensure that SAGE tags and tag counts were comparable between different SAGE libraries all the libraries were normalized to 1,000,000 SAGE tags. Qualitatively, expression profiles of mouse RFX genes obtained from SAGE analysis are consistent with the expression profiles of human RFX genes obtained from the dbEST database analysis, as well as previous publications about human RFX gene expressions (Figure 5). In contrast to all other RFX genes–RFX1-5 and RFX7, which are heavily expressed in the brain, RFX6 is clearly absent from all types of brain tissues (Figure 5). RFX6 is primarily found in the pancreas (Figure 5) which is consistent with results obtained from analyzing dbEST. Low level expression of RFX6 is found in liver (also detected in dbEST) and heart. In addition to the high tissue-specificity, RFX6 has the lowest overall expression level among all seven RFX genes, suggesting that RFX6 may be under tighter regulatory control. In contrast, RFX7 has the highest relative expression level among all seven mouse RFX genes. Similar to RFX1 and RFX5, RFX7 is found in essentially all types of tissues that were examined (Figure 5).

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