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PMID: 12364607 Published · ppublish English Journal Article

Predicting transcription factor synergism.

Nucleic acids research ·Vol. 30 ·No. 19 ·2002-10-01 ·Pages 4278-84

Hannenhalli S, Levy S

Abstract

Transcriptional regulation is mediated by a battery of transcription factor (TF) proteins, that form complexes involving protein-protein and protein-DNA interactions. Individual TFs bind to their cognate cis-elements or transcription factor-binding sites (TFBS). TFBS are organized on the DNA proximal to the gene in groups confined to a few hundred base pair regions. These groups are referred to as modules. Various modules work together to provide the combinatorial regulation of gene transcription in response to various developmental and environmental conditions. The sets of modules constitute a promoter model. Determining the TFs that preferentially work in concert as part of a module is an essential component of understanding transcriptional regulation. The TFs that act synergistically in such a fashion are likely to have their cis-elements co-localized on the genome at specific distances apart. We exploit this notion to predict TF pairs that are likely to be part of a transcriptional module on the human genome sequence. The computational method is validated statistically, using known interacting pairs extracted from the literature. There are 251 TFBS pairs up to 50 bp apart and 70 TFBS pairs up to 200 bp apart that score higher than any of the known synergistic pairs. Further investigation of 50 pairs randomly selected from each of these two sets using PubMed queries provided additional supporting evidence from the existing biological literature suggesting TF synergism for these novel pairs.

MeSH Terms
Algorithms Binding Sites/genetics DNA/genetics,metabolism Gene Expression Regulation Genome, Human Humans Models, Genetic PubMed Transcription Factors/metabolism Transcription, Genetic/genetics
Chemicals
Transcription Factors DNA
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Hannenhalli Sridhar
Informatics Research, Celera Genomics, 45 West Gude Drive, Rockville, MD 20850, USA. [email protected]
Levy Samuel
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkf535
Email
[email protected]
Published
2002-10-01
Pages
4278-84
Language
English
Region
England
NLM ID
0411011
PMCID
PMC140535
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/gkf535 PMC Full Text View journal details
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