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.
Bibliographical noteFunding Information:
We thank Mark Kankel, Mat Sowa, Jean-Francois Rual, and members of S.A.-T.’s lab for helpful discussions and comments. This work was supported by a grant from the NIH (5RO1HG003616) to S.A.-T. Generation of the clone set was supported by a grant from the NHGRI (P41HG3487) to S.E.C. D.-Y.C. and T.M.P. were supported by the Intramural Research Program of the National Library of Medicine, NIH.
© 2014 The Authors.