TFCONES: A database of vertebrate transcription factor-encoding genes and their associated conserved noncoding elements

Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673, Singapore.
BMC Genomics (Impact Factor: 4.04). 02/2007; 8:441. DOI: 10.1186/1471-2164-8-441
Source: PubMed

ABSTRACT Transcription factors (TFs) regulate gene transcription and play pivotal roles in various biological processes such as development, cell cycle progression, cell differentiation and tumor suppression. Identifying cis-regulatory elements associated with TF-encoding genes is a crucial step in understanding gene regulatory networks. To this end, we have used a comparative genomics approach to identify putative cis-regulatory elements associated with TF-encoding genes in vertebrates.
We have created a database named TFCONES (Transcription Factor Genes & Associated COnserved Noncoding ElementS) ( which contains all human, mouse and fugu TF-encoding genes and conserved noncoding elements (CNEs) associated with them. The CNEs were identified by gene-by-gene alignments of orthologous TF-encoding gene loci using MLAGAN. We also predicted putative transcription factor binding sites within the CNEs. A significant proportion of human-fugu CNEs contain experimentally defined binding sites for transcriptional activators and repressors, indicating that a majority of the CNEs may function as transcriptional regulatory elements. The TF-encoding genes that are involved in nervous system development are generally enriched for human-fugu CNEs. Users can retrieve TF-encoding genes and their associated CNEs by conducting a keyword search or by selecting a family of DNA-binding proteins.
The conserved noncoding elements identified in TFCONES represent a catalog of highly prioritized putative cis-regulatory elements of TF-encoding genes and are candidates for functional assay.

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    • "Isolation of NSCs from adult human OB represents an accessible source of neural precursors [4], and is expected to provide an attractive tool for transplantation-based therapy of neurodegenerative diseases that avoids the ethical issues raised by the use of human embryos [5]. An increasing amount of information about the possible roles of transcription factors (TFs) in regulation of various biological processes of NSCs [6], is making it possible to utilize TF gene expression profile to explore variations in proliferation and differentiation potentiality of NSCs. "
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    ABSTRACT: TF genomic markers associated with neurogenesis, proliferation, differentiation, and epigenetic control in human embryonic neural stem cells (hENSC(, and adult human olfactory bulb neural stem cells (OBNSC) were studied by immunohistochemistry (IHC) and DNA microarray. The biological impact of TF gene changes in the examined cell types was estimated using DAVID to specify a different GO class and signaling pathway based on KEGG database. Eleven, and twenty eight TF genes were up-regulated (fold change≤2-39) in OBNSC, and hENSC respectively. KEGG pathway analysis for the up-regulated TF genes revealed significant enrichments for the basal transcription factor pathway, and Notch signaling pathway in OBNSCs, and hENSCs, respectively. Immunofluorescence analysis revealed a significantly greater number of β-tubulin III (TUBB3), MAP, glial fibrillary acidic protein (GFAP), and O4 in hENSC when compared to those in OBNSC. Furthermore, the expression of epigenetic-related TF-genes SMARCC1, TAF12, and UHRF1 increased significantly in OBNSC when compared with hENSC.
    Genomics 10/2012; 101(1). DOI:10.1016/j.ygeno.2012.09.006 · 2.79 Impact Factor
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    • "Among these we sought to identify that subset of genes encoding TFs. Two prior studies relied on the presence of DNA-binding domains as a criteria to identify TF genes (Gray et al., 2004; Lee et al., 2007). Both studies focused on the presence of DNA-binding domains as a criterion though each used a slightly different method to refine their selections. "
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    ABSTRACT: Relative positions of neurons within mature murine pelvic ganglia based on expression of neurotransmitters have been described. However the spatial organization of developing innervation in the murine urogenital tract (UGT) and the gene networks that regulate specification and maturation of neurons within the pelvic ganglia of the lower urinary tract (LUT) are unknown. We used whole-mount immunohistochemistry and histochemical stains to localize neural elements in 15.5 days post coitus (dpc) fetal mice. To identify potential regulatory factors expressed in pelvic ganglia, we surveyed expression patterns for known or probable transcription factors (TF) annotated in the mouse genome by screening a whole-mount in situ hybridization library of fetal UGTs. Of the 155 genes detected in pelvic ganglia, 88 encode TFs based on the presence of predicted DNA-binding domains. Neural crest (NC)-derived progenitors within the LUT were labeled by Sox10, a well-known regulator of NC development. Genes identified were categorized based on patterns of restricted expression in pelvic ganglia, pelvic ganglia and urethral epithelium, or pelvic ganglia and urethral mesenchyme. Gene expression patterns and the distribution of Sox10+, Phox2b+, Hu+, and PGP9.5+ cells within developing ganglia suggest previously unrecognized regional segregation of Sox10+ progenitors and differentiating neurons in early development of pelvic ganglia. Reverse transcription-PCR of pelvic ganglia RNA from fetal and post-natal stages demonstrated that multiple TFs maintain post-natal expression, although Pax3 is extinguished before weaning. Our analysis identifies multiple potential regulatory genes including TFs that may participate in segregation of discrete lineages within pelvic ganglia. The genes identified here are attractive candidate disease genes that may now be further investigated for their roles in malformation syndromes or in LUT dysfunction.
    Frontiers in Neuroscience 09/2012; 6:130. DOI:10.3389/fnins.2012.00130 · 3.70 Impact Factor
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    ABSTRACT: Many conserved secondary structures have been identified within conserved elements in the human genome, but only a small fraction of them are known to be functional RNAs. The evolutionary variations of these conserved secondary structures in human populations and their biological functions have not been fully studied. We searched for polymorphisms within conserved secondary structures and identified a number of SNPs within these elements even though they are highly conserved among species. The density of SNPs in conserved secondary structures is about 65% of that of their flanking, non-conserved, sequences. Classification of sites as stems or as loops/bulges revealed that the density of SNPs in stems is about 62% of that found in loops/bulges. Analysis of derived allele frequency data indicates that sites in stems are under stronger evolutionary constraint than sites in loops/bulges. Intergenic conserved secondary structures tend to associate with transcription factor-encoding genes with genetic distance being the measure of regulator-gene associations. A substantial fraction of intergenic conserved secondary structures overlap characterized binding sites for multiple transcription factors. Strong purifying selection implies that secondary structures are probably important carriers of biological functions for conserved sequences. The overlap between intergenic conserved secondary structures and transcription factor binding sites further suggests that intergenic conserved secondary structures have essential roles in directing gene expression in transcriptional regulation networks.
    BMC Genomics 02/2008; 9:520. DOI:10.1186/1471-2164-9-520 · 4.04 Impact Factor
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