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PMID: 16670430 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Nucleic acids research ·Vol. 34 ·No. 8 ·2006-00-00 ·Pages 2238-46

Zhang C, Xuan Z, Otto S, Hover JR, McCorkle SR, Mandel G, Zhang MQ

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.

MeSH Terms
Animals Base Sequence Binding Sites Conserved Sequence Genomics Humans Mice Promoter Regions, Genetic Rats Repressor Proteins/metabolism Transcription Factors/metabolism
Chemicals
RE1-silencing transcription factor Repressor Proteins Transcription Factors
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Zhang Chaolin
Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Xuan Zhenyu
Otto Stefanie
Hover John R
McCorkle Sean R
Mandel Gail
Zhang Michael Q
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkl248
Published
2006-00-00
Epub
2006-00-02
Pages
2238-46
Language
English
Region
England
NLM ID
0411011
PMCID
PMC1456330
Subset
IM
Grants
NHGRI NIH HHS · R01 HG001696 · United States
NHGRI NIH HHS · HG01696 · United States
External Links
PubMed source DOI: 10.1093/nar/gkl248 PMC Full Text View journal details
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