ArticleBMC bioinformatics2005
Ab initio identification of putative human transcription factor binding sites by comparative genomics.
Article in BMC bioinformatics, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 36 citations in OpenAlex.
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- Simple Shared Motifs (SSM) in conserved region of promoters: a new approach to identify co-regulation patterns.BMC bioinformatics · 2011Article
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- Identification of functional TFAP2A and SP1 binding sites in new TFAP2A-modulated genes.BMC genomics · 2010Article
- Genome-wide survey of microRNA-transcription factor feed-forward regulatory circuits in human.Molecular bioSystems · 2009Article
- Short Promoters in Viral Vectors Drive Selective Expression in Mammalian Inhibitory Neurons, but do not Restrict Activity to Specific Inhibitory Cell-Types.Frontiers in neural circuits · 2009Article
- Positional distribution of human transcription factor binding sites.Nucleic acids research · 2008Article
- c-REDUCE: incorporating sequence conservation to detect motifs that correlate with expression.BMC bioinformatics · 2008Article
- Associating transcription factor-binding site motifs with target GO terms and target genes.Nucleic acids research · 2008Article
- Identification of DNA-binding protein target sequences by physical effective energy functions: free energy analysis of lambda repressor-DNA complexes.BMC structural biology · 2007Article
- Identification of candidate regulatory sequences in mammalian 3' UTRs by statistical analysis of oligonucleotide distributions.BMC bioinformatics · 2007Article
- Comparative genomics and experimental promoter analysis reveal functional liver-specific elements in mammalian hepatic lipase genes.BMC genomics · 2007Article
- The identification of functional motifs in temporal gene expression analysis.Evolutionary bioinformatics online · 2007Article
- A new computational approach to analyze human protein complexes and predict novel protein interactions.Genome biology · 2007Article
- Correlated fragile site expression allows the identification of candidate fragile genes involved in immunity and associated with carcinogenesis.BMC bioinformatics · 2006Article
- A survey of motif discovery methods in an integrated framework.Biology direct · 2006Article
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundUnderstanding transcriptional regulation of gene expression is one of the greatest challenges of modern molecular biology. A central role in this mechanism is played by transcription factors, which typically bind to specific, short DNA sequence motifs usually located in the upstream region of the regulated genes. We discuss here a simple and powerful approach for the ab initio identification of these cis-regulatory motifs. The method we present integrates several elements: human-mouse comparison, statistical analysis of genomic sequences and the concept of coregulation. We apply it to a complete scan of the human genome.
resultsBy using the catalogue of conserved upstream sequences collected in the CORG database we construct sets of genes sharing the same overrepresented motif (short DNA sequence) in their upstream regions both in human and in mouse. We perform this construction for all possible motifs from 5 to 8 nucleotides in length and then filter the resulting sets looking for two types of evidence of coregulation: first, we analyze the Gene Ontology annotation of the genes in the set, searching for statistically significant common annotations; second, we analyze the expression profiles of the genes in the set as measured by microarray experiments, searching for evidence of coexpression. The sets which pass one or both filters are conjectured to contain a significant fraction of coregulated genes, and the upstream motifs characterizing the sets are thus good candidates to be the binding sites of the TF's involved in such regulation. In this way we find various known motifs and also some new candidate binding sites.
conclusionWe have discussed a new integrated algorithm for the "ab initio" identification of transcription factor binding sites in the human genome. The method is based on three ingredients: comparative genomics, overrepresentation, different types of coregulation. The method is applied to a full-scan of the human genome, giving satisfactory results.
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