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Wide-Scale Analysis of Human Functional Transcription Factor Binding Reveals a Strong Bias towards the Transcription Start Site
- Source :
- PLoS ONE, Vol 2, Iss 8, p e807 (2007), PLoS ONE
- Publication Year :
- 2008
- Publisher :
- arXiv, 2008.
-
Abstract
- We introduce a novel method to screen the promoters of a set of genes with shared biological function, against a precompiled library of motifs, and find those motifs which are statistically over-represented in the gene set. The gene sets were obtained from the functional Gene Ontology (GO) classification; for each set and motif we optimized the sequence similarity score threshold, independently for every location window (measured with respect to the TSS), taking into account the location dependent nucleotide heterogeneity along the promoters of the target genes. We performed a high throughput analysis, searching the promoters (from 200bp downstream to 1000bp upstream the TSS), of more than 8000 human and 23,000 mouse genes, for 134 functional Gene Ontology classes and for 412 known DNA motifs. When combined with binding site and location conservation between human and mouse, the method identifies with high probability functional binding sites that regulate groups of biologically related genes. We found many location-sensitive functional binding events and showed that they clustered close to the TSS. Our method and findings were put to several experimental tests. By allowing a "flexible" threshold and combining our functional class and location specific search method with conservation between human and mouse, we are able to identify reliably functional TF binding sites. This is an essential step towards constructing regulatory networks and elucidating the design principles that govern transcriptional regulation of expression. The promoter region proximal to the TSS appears to be of central importance for regulation of transcription in human and mouse, just as it is in bacteria and yeast.<br />Comment: 31 pages, including Supplementary Information and figures
- Subjects :
- Gene prediction
Molecular Networks (q-bio.MN)
CAAT box
Computational Biology/Transcriptional Regulation
lcsh:Medicine
Biology
Quantitative Biology - Quantitative Methods
Molecular Biology/Bioinformatics
Mice
Molecular Biology/Translational Regulation
Animals
Humans
Quantitative Biology - Molecular Networks
Binding site
Promoter Regions, Genetic
lcsh:Science
Gene
Transcription factor
Cell Biology/Gene Expression
Quantitative Methods (q-bio.QM)
Genetics
Computational Biology/Systems Biology
Binding Sites
Multidisciplinary
Cell Cycle
lcsh:R
Genetics and Genomics/Gene Expression
Promoter
TATA Box
DNA binding site
FOS: Biological sciences
Computational Biology/Sequence Motif Analysis
lcsh:Q
Mathematics/Statistics
Transcription Initiation Site
TRANSFAC
Research Article
Transcription Factors
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- PLoS ONE, Vol 2, Iss 8, p e807 (2007), PLoS ONE
- Accession number :
- edsair.doi.dedup.....3a7476ceb31fea2638617a6e9778ab76
- Full Text :
- https://doi.org/10.48550/arxiv.0811.1289