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Characterization of the human RFX transcription factor family by regulatory and target gene analysis Sugiaman-Trapman, Debora; Vitezic, Morana; Jouhilahti, Eeva-Mari; Mathelier, Anthony; Lauter, Gilbert; Misra, Sougat; Daub, Carsten O; Kere, Juha; Swoboda, Peter

Abstract

Background: Evolutionarily conserved RFX transcription factors (TFs) regulate their target genes through a DNA sequence motif called the X-box. Thereby they regulate cellular specialization and terminal differentiation. Here, we provide a comprehensive analysis of all the eight human RFX genes (RFX1–8), their spatial and temporal expression profiles, potential upstream regulators and target genes. Results: We extracted all known human RFX1–8 gene expression profiles from the FANTOM5 database derived from transcription start site (TSS) activity as captured by Cap Analysis of Gene Expression (CAGE) technology. RFX genes are broadly (RFX1–3, RFX5, RFX7) and specifically (RFX4, RFX6) expressed in different cell types, with high expression in four organ systems: immune system, gastrointestinal tract, reproductive system and nervous system. Tissue type specific expression profiles link defined RFX family members with the target gene batteries they regulate. We experimentally confirmed novel TSS locations and characterized the previously undescribed RFX8 to be lowly expressed. RFX tissue and cell type specificity arises mainly from differences in TSS architecture. RFX transcript isoforms lacking a DNA binding domain (DBD) open up new possibilities for combinatorial target gene regulation. Our results favor a new grouping of the RFX family based on protein domain composition. We uncovered and experimentally confirmed the TFs SP2 and ESR1 as upstream regulators of specific RFX genes. Using TF binding profiles from the JASPAR database, we determined relevant patterns of X-box motif positioning with respect to gene TSS locations of human RFX target genes. Conclusions: The wealth of data we provide will serve as the basis for precisely determining the roles RFX TFs play in human development and disease.

Item Metadata

Title
Characterization of the human RFX transcription factor family by regulatory and target gene analysis
Creator
Sugiaman-Trapman, Debora; Vitezic, Morana; Jouhilahti, Eeva-Mari; Mathelier, Anthony; Lauter, Gilbert; Misra, Sougat; Daub, Carsten O; Kere, Juha; Swoboda, Peter
Contributor
University of British Columbia. Centre for Molecular Medicine and Therapeutics; Child and Family Research Institute
Publisher
BioMed Central
Date Issued
2018-03-06
Description
Background: Evolutionarily conserved RFX transcription factors (TFs) regulate their target genes through a DNA sequence motif called the X-box. Thereby they regulate cellular specialization and terminal differentiation. Here, we provide a comprehensive analysis of all the eight human RFX genes (RFX1–8), their spatial and temporal expression profiles, potential upstream regulators and target genes. Results: We extracted all known human RFX1–8 gene expression profiles from the FANTOM5 database derived from transcription start site (TSS) activity as captured by Cap Analysis of Gene Expression (CAGE) technology. RFX genes are broadly (RFX1–3, RFX5, RFX7) and specifically (RFX4, RFX6) expressed in different cell types, with high expression in four organ systems: immune system, gastrointestinal tract, reproductive system and nervous system. Tissue type specific expression profiles link defined RFX family members with the target gene batteries they regulate. We experimentally confirmed novel TSS locations and characterized the previously undescribed RFX8 to be lowly expressed. RFX tissue and cell type specificity arises mainly from differences in TSS architecture. RFX transcript isoforms lacking a DNA binding domain (DBD) open up new possibilities for combinatorial target gene regulation. Our results favor a new grouping of the RFX family based on protein domain composition. We uncovered and experimentally confirmed the TFs SP2 and ESR1 as upstream regulators of specific RFX genes. Using TF binding profiles from the JASPAR database, we determined relevant patterns of X-box motif positioning with respect to gene TSS locations of human RFX target genes. Conclusions: The wealth of data we provide will serve as the basis for precisely determining the roles RFX TFs play in human development and disease.
Subject
Cell differentiation; Cilia; Spermatogenesis; Immune cell proliferation; Neuronal development; Cell cycle control; Tumor suppression
Genre
Article
Type
Text
Language
eng
Date Available
2018-03-07
Provider
Vancouver : University of British Columbia Library
Rights
Attribution 4.0 International (CC BY 4.0)
DOI
10.14288/1.0364165
URI
http://hdl.handle.net/2429/64759
Affiliation
Medicine, Faculty of; Other UBC; Non UBC; Medical Genetics, Department of
Citation
BMC Genomics. 2018 Mar 06;19(1):181
Publisher DOI
10.1186/s12864-018-4564-6
Peer Review Status
Reviewed
Scholarly Level
Faculty
Copyright Holder
The Author(s).
Rights URI
http://creativecommons.org/licenses/by/4.0/
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Attribution 4.0 International (CC BY 4.0)