Department of Molecular Genetics, University of Toronto, Toronto, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada
Ann Boija
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden
Edvin Karlsson
Department of Molecular Biology, Umeå University, Umeå, Sweden; Division of CBRN Security and Defence, FOI-Swedish Defence Research Agency, Umeå, Sweden
Per-Henrik Holmqvist
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden
Yonit Tsatskis
Department of Molecular Genetics, University of Toronto, Toronto, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada
Ilaria Nisoli
Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King’s College London, London, United Kingdom
Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada
Alireza Lorzadeh
Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada; Michael Smith Laboratories, Vancouver, Canada; Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, Canada
Michelle Moksa
Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada; Michael Smith Laboratories, Vancouver, Canada; Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, Canada
Martin Hirst
Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada; Michael Smith Laboratories, Vancouver, Canada; Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, Canada
Samuel Aparicio
Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada
Manolis Fanto
Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King’s College London, London, United Kingdom
Per Stenberg
Department of Molecular Biology, Umeå University, Umeå, Sweden; Division of CBRN Security and Defence, FOI-Swedish Defence Research Agency, Umeå, Sweden
Mattias Mannervik
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden
Department of Molecular Genetics, University of Toronto, Toronto, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada
Mutations in human Atrophin1, a transcriptional corepressor, cause dentatorubral-pallidoluysian atrophy, a neurodegenerative disease. Drosophila Atrophin (Atro) mutants display many phenotypes, including neurodegeneration, segmentation, patterning and planar polarity defects. Despite Atro’s critical role in development and disease, relatively little is known about Atro’s binding partners and downstream targets. We present the first genomic analysis of Atro using ChIP-seq against endogenous Atro. ChIP-seq identified 1300 potential direct targets of Atro including engrailed, and components of the Dpp and Notch signaling pathways. We show that Atro regulates Dpp and Notch signaling in larval imaginal discs, at least partially via regulation of thickveins and fringe. In addition, bioinformatics analyses, sequential ChIP and coimmunoprecipitation experiments reveal that Atro interacts with the Drosophila GAGA Factor, Trithorax-like (Trl), and they bind to the same loci simultaneously. Phenotypic analyses of Trl and Atro clones suggest that Atro is required to modulate the transcription activation by Trl in larval imaginal discs. Taken together, these data indicate that Atro is a major Trl cofactor that functions to moderate developmental gene transcription.
