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Combinatorial interactions among transcription factors (TFs) play essential roles in generating gene expression specificity and diversity in metazoans. Using yeast 2-hybrid (Y2H) assays on nearly all sequence-specific Drosophila TFs, we identified 1,983 protein-protein interactions (PPIs), more than doubling the number of currently known PPIs among Drosophila TFs. For quality assessment, we validated a subset of our interactions using MITOMI and bimolecular fluorescence complementation assays. We combined our interactome with prior PPI data to generate an integrated Drosophila TF-TF binary interaction network. Our analysis of ChIP-seq data, integrating PPI and gene expression information, uncovered different modes by which interacting TFs are recruited to DNA. We further demonstrate the utility of our Drosophila interactome in shedding light on human TF-TF interactions. This study reveals how TFs interact to bind regulatory elements in vivo and serves as a resource of Drosophila TF-TF binary PPIs for understanding tissue-specific gene regulation.

Original publication

DOI

10.1016/j.celrep.2019.03.071

Type

Journal article

Journal

Cell Rep

Publication Date

16/04/2019

Volume

27

Pages

955 - 970.e7

Keywords

BiFC, ChIP-seq analysis, Drosophila melanogaster, MITOMI, in vivo bimolecular fluorescence complementation assay, protein-protein interactions, transcription factor-DNA interactions, transcription factors, yeast two-hybrid