A Myc-Groucho complex integrates EGF and Notch signaling to regulate neural development.
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.
Orian
Amir
A
Division of Basic Sciences, Genomic Resource, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. mdoryan@techunix.technion.ac.il
Delrow
Jeffrey J
JJ
Rosales Nieves
Alicia E
AE
Abed
Mona
M
Metzger
David
D
Paroush
Ze'ev
Z
Eisenman
Robert N
RN
Parkhurst
Susan M
SM
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000502:physiology*; D002843:Chromatin / Q000235:genetics; D004330:Drosophila / Q000196:embryology / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000502:physiology; D066246:ErbB Receptors / Q000502:physiology*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D016259:Genes, myc; D009420:Nervous System / Q000196:embryology; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific) / Q000235:genetics; D014158:Transcription, Genetic
D051792:Basic Helix-Loop-Helix Proteins; D002843:Chromatin; D066246:ErbB Receptors; D012097:Repressor Proteins; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific); C091023:gro protein, Drosophila