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Cell Rep. 2014 Sep 25;8(6):2031-2043. doi: 10.1016/j.celrep.2014.08.038. Epub 2014 Sep 18.

Transcription factor networks in Drosophila melanogaster.

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Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
Institute for Genomics and Systems Biology, University of Chicago, Chicago, IL 60637, USA.
Berkeley Drosophila Genome Project, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA; Biogen Idec, Inc., Cambridge, MA 02142, USA. Electronic address:


Specific cellular fates and functions depend on differential gene expression, which occurs primarily at the transcriptional level and is controlled by complex regulatory networks of transcription factors (TFs). TFs act through combinatorial interactions with other TFs, cofactors, and chromatin-remodeling proteins. Here, we define protein-protein interactions using a coaffinity purification/mass spectrometry method and study 459 Drosophila melanogaster transcription-related factors, representing approximately half of the established catalog of TFs. We probe this network in vivo, demonstrating functional interactions for many interacting proteins, and test the predictive value of our data set. Building on these analyses, we combine regulatory network inference models with physical interactions to define an integrated network that connects combinatorial TF protein interactions to the transcriptional regulatory network of the cell. We use this integrated network as a tool to connect the functional network of genetic modifiers related to mastermind, a transcriptional cofactor of the Notch pathway.

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