ArticleNucleic acids research2014
Constrained transcription factor spacing is prevalent and important for transcriptional control of mouse blood cells.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
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- A single ChIP-seq dataset is sufficient for comprehensive analysis of motifs co-occurrence with MCOT package.Nucleic acids research · 2019Article
- A De Novo Shape Motif Discovery Algorithm Reveals Preferences of Transcription Factors for DNA Shape Beyond Sequence Motifs.Cell systems · 2019Article
- Exploiting genetic variation to uncover rules of transcription factor binding and chromatin accessibility.Nature communications · 2018Article
- A graphical model approach visualizes regulatory relationships between genome-wide transcription factor binding profiles.Briefings in bioinformatics · 2018Article
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- Spatial distribution of predicted transcription factor binding sites in Drosophila ChIP peaks.Mechanisms of development · 2016Article
- Nucleotide Interdependency in Transcription Factor Binding Sites in the Drosophila Genome.Gene regulation and systems biology · 2016Article
- The DEK Oncoprotein Is a Critical Component of the EKLF/KLF1 Enhancer in Erythroid Cells.Molecular and cellular biology · 2015Article
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7 authors at 1 institution in 1 country.
Funding
Abstract
Combinatorial transcription factor (TF) binding is essential for cell-type-specific gene regulation. However, much remains to be learned about the mechanisms of TF interactions, including to what extent constrained spacing and orientation of interacting TFs are critical for regulatory element activity. To examine the relative prevalence of the 'enhanceosome' versus the 'TF collective' model of combinatorial TF binding, a comprehensive analysis of TF binding site sequences in large scale datasets is necessary. We developed a motif-pair discovery pipeline to identify motif co-occurrences with preferential distance(s) between motifs in TF-bound regions. Utilizing a compendium of 289 mouse haematopoietic TF ChIP-seq datasets, we demonstrate that haematopoietic-related motif-pairs commonly occur with highly conserved constrained spacing and orientation between motifs. Furthermore, motif clustering revealed specific associations for both heterotypic and homotypic motif-pairs with particular haematopoietic cell types. We also showed that disrupting the spacing between motif-pairs significantly affects transcriptional activity in a well-known motif-pair-E-box and GATA, and in two previously unknown motif-pairs with constrained spacing-Ets and Homeobox as well as Ets and E-box. In this study, we provide evidence for widespread sequence-specific TF pair interaction with DNA that conforms to the 'enhanceosome' model, and furthermore identify associations between specific haematopoietic cell-types and motif-pairs.
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