Document Detail

Uncovering cis-regulatory sequence requirements for context-specific transcription factor binding.
MedLine Citation:
PMID:  22534400     Owner:  NLM     Status:  MEDLINE    
The regulation of gene expression is mediated at the transcriptional level by enhancer regions that are bound by sequence-specific transcription factors (TFs). Recent studies have shown that the in vivo binding sites of single TFs differ between developmental or cellular contexts. How this context-specific binding is encoded in the cis-regulatory DNA sequence has, however, remained unclear. We computationally dissect context-specific TF binding sites in Drosophila, Caenorhabditis elegans, mouse, and human and find distinct combinations of sequence motifs for partner factors, which are predictive and reveal specific motif requirements of individual binding sites. We predict that TF binding in the early Drosophila embryo depends on motifs for the early zygotic TFs Vielfaltig (also known as Zelda) and Tramtrack. We validate experimentally that the activity of Twist-bound enhancers and Twist binding itself depend on Vielfaltig motifs, suggesting that Vielfaltig is more generally important for early transcription. Our finding that the motif content can predict context-specific binding and that the predictions work across different Drosophila species suggests that characteristic motif combinations are shared between sites, revealing context-specific motif codes (cis-regulatory signatures), which appear to be conserved during evolution. Taken together, this study establishes a novel approach to derive predictive cis-regulatory motif requirements for individual TF binding sites and enhancers. Importantly, the method is generally applicable across different cell types and organisms to elucidate cis-regulatory sequence determinants and the corresponding trans-acting factors from the increasing number of tissue- and cell-type-specific TF binding studies.
J Omar Yáñez-Cuna; Huy Q Dinh; Evgeny Z Kvon; Daria Shlyueva; Alexander Stark
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-04-25
Journal Detail:
Title:  Genome research     Volume:  22     ISSN:  1549-5469     ISO Abbreviation:  Genome Res.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-02     Completed Date:  2013-02-19     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  9518021     Medline TA:  Genome Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2018-30     Citation Subset:  IM    
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MeSH Terms
Binding Sites*
Chromatin Immunoprecipitation
Computational Biology / methods*
Drosophila / genetics
Gene Expression Regulation
High-Throughput Nucleotide Sequencing
Nucleotide Motifs*
Protein Binding
Regulatory Sequences, Nucleic Acid*
Transcription Factors / metabolism*
Grant Support
242922//European Research Council
Reg. No./Substance:
0/Transcription Factors

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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