A clustering property of highly-degenerate transcription factor binding sites in the mammalian genome

Chaolin Zhang, Zhenyu Xuan, Stefanie Otto, John R. Hover, Sean R. McCorkle, Gail Mandel, Michael Q. Zhang

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Transcription factor binding sites (TFBSs) are short DNA sequences interacting with transcription factors (TFs), which regulate gene expression. Due to the relatively short length of such binding sites, it is largely unclear how the specificity of protein-DNA interaction is achieved. Here, we have performed a genome-wide analysis of TFBS-like sequences for the transcriptional repressor, RE1 Silencing Transcription Factor (REST), as well as for several other representative mammalian TFs (c-myc, p53, HNF-1 and CREB). We find a nonrandom distribution of inexact sites for these TFs, referred to as highly-degenerate TFBSs, that are enriched around the cognate binding sites. Comparisons among human, mouse and rat orthologous promoters reveal that these highly-degenerate sites are conserved significantly more than expected by random chance, suggesting their positive selection during evolution. We propose that this arrangement provides a favorable genomic landscape for functional target site selection.

Original languageEnglish (US)
Pages (from-to)2238-2246
Number of pages9
JournalNucleic Acids Research
Volume34
Issue number8
DOIs
StatePublished - 2006
Externally publishedYes

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Cluster Analysis
Transcription Factors
Binding Sites
Genome
Gene Expression
DNA
Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

A clustering property of highly-degenerate transcription factor binding sites in the mammalian genome. / Zhang, Chaolin; Xuan, Zhenyu; Otto, Stefanie; Hover, John R.; McCorkle, Sean R.; Mandel, Gail; Zhang, Michael Q.

In: Nucleic Acids Research, Vol. 34, No. 8, 2006, p. 2238-2246.

Research output: Contribution to journalArticle

Zhang, Chaolin ; Xuan, Zhenyu ; Otto, Stefanie ; Hover, John R. ; McCorkle, Sean R. ; Mandel, Gail ; Zhang, Michael Q. / A clustering property of highly-degenerate transcription factor binding sites in the mammalian genome. In: Nucleic Acids Research. 2006 ; Vol. 34, No. 8. pp. 2238-2246.
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