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Nucleic Acids Research Advance Access published online on October 25, 2008
Nucleic Acids Research, doi:10.1093/nar/gkn752
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© 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.

Gene Regulation, Chromatin And Epigenetics

Positional distribution of human transcription factor binding sites

Mark Koudritsky and Eytan Domany*

Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot 76100, Israel

*To whom correspondence should be addressed. Tel: +972 8 9343964; Fax: +972 8 9344109; Email: eytan.domany{at}weizmann.ac.il

Received April 29, 2008. Revised September 30, 2008. Accepted October 5, 2008.

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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