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CCAT: Combinatorial Code Analysis Tool for transcriptional regulation

Author(s): Jiang, P; Singh, Mona

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Abstract: Combinatorial interplay among transcription factors (TFs) is an important mechanism by which transcriptional regulatory specificity is achieved. However, despite the increasing number of TFs for which either binding specificities or genome-wide occupancy data are known, knowledge about cooperativity between TFs remains limited. To address this, we developed a computational framework for predicting genome-wide co-binding between TFs (CCAT, Combinatorial Code Analysis Tool), and applied it to Drosophila melanogaster to uncover cooperativity among TFs during embryo development. Using publicly available TF binding specificity data and DNaseI chromatin accessibility data, we first predicted genome-wide binding sites for 324 TFs across five stages of D. melanogaster embryo development. We then applied CCAT in each of these developmental stages, and identified from 19 to 58 pairs of TFs in each stage whose predicted binding sites are significantly co-localized. We found that nearby binding sites for pairs of TFs predicted to cooperate were enriched in regions bound in relevant ChIP experiments, and were more evolutionarily conserved than other pairs. Further, we found that TFs tend to be co-localized with other TFs in a dynamic manner across developmental stages.
Publication Date: 22-Dec-2013
Electronic Publication Date: 1-Mar-2014
Citation: Jiang, P, Singh, M. (2014). CCAT: Combinatorial Code Analysis Tool for transcriptional regulation. Nucleic Acids Research, 42 (2833 - 2847. doi:10.1093/nar/gkt1302
DOI: doi:10.1093/nar/gkt1302
Pages: 2833 - 2847
Type of Material: Journal Article
Journal/Proceeding Title: Nucleic Acids Research
Version: Final published version. This is an open access article.

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