Abstract
Recognition of composite elements consisting of two transcription factor binding sites gets behind the studies of tissue-, stage- and condition-specific transcription. Genome-wide data on transcription factor binding generated with ChIP-seq method facilitate an identification of composite elements, but the existing bioinformatics tools either require ChIP-seq datasets for both partner transcription factors, or omit composite elements with motifs overlapping. Here we present an universal Motifs Co-Occurrence Tool (MCOT) that retrieves maximum information about overrepresented composite elements from a single ChIP-seq dataset. This includes homo- and heterotypic composite elements of four mutual orientations of motifs, separated with a spacer or overlapping, even if recognition of motifs within composite element requires various stringencies. Analysis of 52 ChIP-seq datasets for 18 human transcription factors confirmed that for over 60% of analyzed datasets and transcription factors predicted co-occurrence of motifs implied experimentally proven protein-protein interaction of respecting transcription factors. Analysis of 164 ChIP-seq datasets for 57 mammalian transcription factors showed that abundance of predicted composite elements with an overlap of motifs compared to those with a spacer more than doubled; and they had 1.5-fold increase of asymmetrical pairs of motifs with one more conservative 'leading' motif and another one 'guided'.
Original language | English |
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Pages (from-to) | e139 |
Number of pages | 14 |
Journal | Nucleic Acids Research |
Volume | 47 |
Issue number | 21 |
DOIs | |
Publication status | Published - 2 Dec 2019 |
Keywords
- Algorithms
- Animals
- Binding Sites
- Chromatin Immunoprecipitation Sequencing/methods
- Computational Biology/methods
- Datasets as Topic
- Humans
- Mice
- Nucleotide Motifs/genetics
- Regulatory Elements, Transcriptional/genetics
- Sequence Analysis, DNA/methods
- Transcription Factors/genetics
- TRANSCRIPTION FACTORS
- ACTIVATION
- DNA-BINDING
- CHROMATIN
- COMPLEXES
- COMPOSITE REGULATORY ELEMENTS
- ENHANCERS
- DISCOVERY
- REGIONS
- NF-KAPPA-B