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Nucleic Acids Res. 2014 Mar;42(5):2833-47. doi: 10.1093/nar/gkt1302. Epub 2013 Dec 23.

CCAT: Combinatorial Code Analysis Tool for transcriptional regulation.

Author information

1
Department of Computer Science, Princeton University, Princeton, 08540 NJ, USA and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, 08544 NJ, USA.

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. All generated data as well as source code for our front-to-end pipeline are available at http://cat.princeton.edu.

PMID:
24366875
PMCID:
PMC3950699
DOI:
10.1093/nar/gkt1302
[Indexed for MEDLINE]
Free PMC Article

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