Transcription Factor Networks in Drosophila melanogaster
David Y. Rhee,
Dong-Yeon Cho,
Bo Zhai,
Matthew Slattery,
Lijia Ma,
Julian Mintseris,
Christina Y. Wong,
Kevin P. White,
Susan E. Celniker,
Teresa M. Przytycka,
Steven P. Gygi,
Robert A. Obar,
Spyros Artavanis-Tsakonas
Affiliations
David Y. Rhee
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Dong-Yeon Cho
Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA
Bo Zhai
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Matthew Slattery
Institute for Genomics and Systems Biology, University of Chicago, Chicago, IL 60637, USA
Lijia Ma
Institute for Genomics and Systems Biology, University of Chicago, Chicago, IL 60637, USA
Julian Mintseris
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Christina Y. Wong
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Kevin P. White
Institute for Genomics and Systems Biology, University of Chicago, Chicago, IL 60637, USA
Susan E. Celniker
Berkeley Drosophila Genome Project, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
Teresa M. Przytycka
Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA
Steven P. Gygi
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Robert A. Obar
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Spyros Artavanis-Tsakonas
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
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.
