ArticleGenome research2012
Uncovering cis-regulatory sequence requirements for context-specific transcription factor binding.
Article in Genome research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed.
- Differential usage of two, distinct DNA-binding domains regulates tissue-specific occupancy of the pioneer factor Zelda.bioRxiv : the preprint server for biology · 2025Article
- Bulk-level maps of pioneer factor binding dynamics during the Drosophila maternal-to-zygotic transition.Development (Cambridge, England) · 2025Article
- Catalytic-dependent and independent functions of the histone acetyltransferase CBP promote pioneer-factor-mediated zygotic genome activation.Molecular cell · 2025Article
- Crosstalk between paralogs and isoforms influences p63-dependent regulatory element activity.Nucleic acids research · 2024Article
- Global coupling of R-loop dynamics with RNA polymerase II modulates gene expression and early development of Drosophila.Nucleic acids research · 2024Article
- Repeated Shifts in Sociality Are Associated With Fine-tuning of Highly Conserved and Lineage-Specific Enhancers in a Socially Flexible Bee.Molecular biology and evolution · 2024Article
- Systematic dissection of sequence features affecting binding specificity of a pioneer factor reveals binding synergy between FOXA1 and AP-1.Molecular cell · 2024Article
- Context dependent activity of p63-bound gene regulatory elements.bioRxiv : the preprint server for biology · 2024Article
- Protein-intrinsic properties and context-dependent effects regulate pioneer factor binding and function.Nature structural & molecular biology · 2024Article
- Multiomics-integrated deep language model enables in silico genome-wide detection of transcription factor binding site in unexplored biosamples.Bioinformatics (Oxford, England) · 2024Article
- Chromatin accessibility in the Drosophila embryo is determined by transcription factor pioneering and enhancer activation.Developmental cell · 2023Article
- Review
- Protein-intrinsic properties and context-dependent effects regulate pioneer-factor binding and function.bioRxiv : the preprint server for biology · 2023Article
- Prediction accuracy of regulatory elements from sequence varies by functional sequencing technique.Frontiers in cellular and infection microbiology · 2023Article
- DeepSTARR predicts enhancer activity from DNA sequence and enables the de novo design of synthetic enhancers.Nature genetics · 2022Article
- TheFaculty reviews · 2022Review
- Article
- Spatial organization of transcribing loci during early genome activation in Drosophila.Current biology : CB · 2021Article
- The non-coding genome in genetic brain disorders: new targets for therapy?Essays in biochemistry · 2021Review
- Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
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.
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