| Uncovering cis-regulatory sequence requirements for context-specific transcription factor binding. | |
| | |
MedLine Citation:
|
PMID: 22534400 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
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: 2013-02-28 |
Medline Journal Info:
|
Nlm Unique ID: 9518021 Medline TA: Genome Res Country: United States |
Other Details:
|
Languages: eng Pagination: 2018-30 Citation Subset: IM |
Affiliation:
|
Research Institute of Molecular Pathology, 1030 Vienna, Austria. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Binding Sites* Chromatin Immunoprecipitation Computational Biology / methods* Drosophila / genetics Gene Expression Regulation High-Throughput Nucleotide Sequencing Humans Mice Nucleotide Motifs* Protein Binding Regulatory Sequences, Nucleic Acid* Transcription Factors / metabolism* |
| Chemical | |
Reg. No./Substance:
|
0/Transcription Factors |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Global analysis reveals multiple pathways for unique regulation of mRNA decay in induced pluripotent...
Next Document: Citalopram-induced subacute cutaneous lupus erythematosus - first case and review concerning photose...