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      Positional distribution of human transcription factor binding sites

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      Nucleic Acids Research
      Oxford University Press

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          Abstract

          We developed a method for estimating the positional distribution of transcription factor (TF) binding sites using ChIP-chip data, and applied it to recently published experiments on binding sites of nine TFs: OCT4, SOX2, NANOG, HNF1A, HNF4A, HNF6, FOXA2, USF1 and CREB1. The data were obtained from a genome-wide coverage of promoter regions from 8-kb upstream of the transcription start site (TSS) to 2-kb downstream. The number of target genes of each TF ranges from few hundred to several thousand. We found that for each of the nine TFs the estimated binding site distribution is closely approximated by a mixture of two components: a narrow peak, localized within 300-bp upstream of the TSS, and a distribution of almost uniform density within the tested region. Using Gene Ontology (GO) and Enrichment analysis, we were able to associate (for each of the TFs studied) the target genes of both types of binding with known biological processes. Most GO terms were enriched either among the proximal targets or among those with a uniform distribution of binding sites. For example, the three stemness-related TFs have several hundred target genes that belong to ‘development’ and ‘morphogenesis’ whose binding sites belong to the uniform distribution.

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          Most cited references18

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            Gene Ontology: tool for the unification of biology

            Genomic sequencing has made it clear that a large fraction of the genes specifying the core biological functions are shared by all eukaryotes. Knowledge of the biological role of such shared proteins in one organism can often be transferred to other organisms. The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing. To this end, three independent ontologies accessible on the World-Wide Web (http://www.geneontology.org) are being constructed: biological process, molecular function and cellular component.
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              TRANSFAC: transcriptional regulation, from patterns to profiles.

              The TRANSFAC database on eukaryotic transcriptional regulation, comprising data on transcription factors, their target genes and regulatory binding sites, has been extended and further developed, both in number of entries and in the scope and structure of the collected data. Structured fields for expression patterns have been introduced for transcription factors from human and mouse, using the CYTOMER database on anatomical structures and developmental stages. The functionality of Match, a tool for matrix-based search of transcription factor binding sites, has been enhanced. For instance, the program now comes along with a number of tissue-(or state-)specific profiles and new profiles can be created and modified with Match Profiler. The GENE table was extended and gained in importance, containing amongst others links to LocusLink, RefSeq and OMIM now. Further, (direct) links between factor and target gene on one hand and between gene and encoded factor on the other hand were introduced. The TRANSFAC public release is available at http://www.gene-regulation.com. For yeast an additional release including the latest data was made available separately as TRANSFAC Saccharomyces Module (TSM) at http://transfac.gbf.de. For CYTOMER free download versions are available at http://www.biobase.de:8080/index.html.
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                Author and article information

                Journal
                Nucleic Acids Res
                Nucleic Acids Res
                nar
                nar
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                December 2008
                25 October 2008
                25 October 2008
                : 36
                : 21
                : 6795-6805
                Affiliations
                Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot 76100, Israel
                Author notes
                *To whom correspondence should be addressed. Tel: +972 8 9343964; Fax: +972 8 9344109; Email: eytan.domany@ 123456weizmann.ac.il
                Article
                gkn752
                10.1093/nar/gkn752
                2588498
                18953043
                2c4a32bb-6153-4176-9aa3-38608d5f1189
                © 2008 The Author(s)

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 April 2008
                : 30 September 2008
                : 5 October 2008
                Categories
                Gene regulation, Chromatin and Epigenetics

                Genetics
                Genetics

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