Atrophin controls developmental signaling pathways via interactions with Trithorax-like
- University of Toronto, Canada
- Stockholm University, Sweden
- Umeå University, Sweden
- University College London, United Kingdom
- University of British Columbia, Canada
- King's College London, United Kingdom
Abstract
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 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.
Data availability
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ChIP-seq of Atrophin in Drosophila S2 cellsPublicly available at the NCBI Gene (accession no: GSE87509).
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Atrophin (Atro) ChIP-seq data from Drosophila S2 cellsPublicly available at the NCBI Gene (accession no: GSE87471).
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Chromatin Binding Site Mapping of Transcription Factors in D. melanogaster by ChIP-seqPublicly available at Modencode (http://intermine.modencode.org).
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Chromatin Binding Site MappingPublicly available at Modencode (http://intermine.modencode.org).
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The Genomic Binding Profile of GAGA Element Associated Factor (GAF) in Drosophila S2 cellsPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE40646).
Article and author information
Author details
Funding
Canadian Institutes of Health Research (FDN 143319)
- Helen McNeill
Medical Research Council (NIRG-G1002186)
- Manolis Fanto
Knut och Alice Wallenbergs Stiftelse
- Per Stenberg
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- K VijayRaghavan, National Centre for Biological Sciences, Tata Institute of Fundamental Research, India
Version history
- Received: November 8, 2016
- Accepted: March 15, 2017
- Accepted Manuscript published: March 22, 2017 (version 1)
- Version of Record published: April 28, 2017 (version 2)
Copyright
© 2017, Yeung et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Atrophin controls developmental signaling pathways via interactions with Trithorax-like
eLife 6:e23084.
https://doi.org/10.7554/eLife.23084
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