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A Myc-Groucho complex integrates EGF and Notch signaling to regulate neural development

TitleA Myc-Groucho complex integrates EGF and Notch signaling to regulate neural development
Publication TypeJournal Article
Year of Publication2007
AuthorsOrian A, Delrow JJ, Rosales Nieves AE, Abed M, Metzger D, Paroush Z, Eisenman RN, Parkhurst SM
JournalProc Natl Acad Sci U S A
Date Published2007
ISBN Number0027-8424 (Print)0027-8424 (Linking)
Keywords*Genes, myc, Gene Expression Profiling, Animals, Basic Helix-Loop-Helix Transcription Factors/genetics/*physiology, Chromatin/genetics, Drosophila/embryology/genetics, Embryo, Nonmammalian/physiology, Gene Expression Regulation, Developmental, Nervous System/embryology, Receptor, Epidermal Growth Factor/*physiology, Repressor Proteins/genetics/*physiology, Signal Transduction, Site-Specific DNA-Methyltransferase (Adenine-Specific)/genetics, Transcription, Genetic

Integration of patterning cues via transcriptional networks to coordinate gene expression is critical during morphogenesis and misregulated in cancer. Using DNA adenine methyltransferase (Dam)ID chromatin profiling, we identified a protein-protein interaction between the Drosophila Myc oncogene and the Groucho corepressor that regulates a subset of direct dMyc targets. Most of these shared targets affect fate or mitosis particularly during neurogenesis, suggesting the dMyc-Groucho complex may coordinate fate acquisition with mitotic capacity during development. We find an antagonistic relationship between dMyc and Groucho that mimics the antagonistic interactions found for EGF and Notch signaling: dMyc is required to specify neuronal fate and enhance neuroblast mitosis, whereas Groucho is required to maintain epithelial fate and inhibit mitosis. Our results suggest that the dMyc-Groucho complex defines a previously undescribed mechanism of Myc function and may serve as the transcriptional unit that integrates EGF and Notch inputs to regulate early neuronal development.