Damage-responsive, maturity-silenced enhancers regulate multiple genes that direct regeneration in Drosophila
Abstract
Like tissues of many organisms, Drosophila imaginal discs lose the ability to regenerate as they mature. This loss of regenerative capacity coincides with reduced damage-responsive expression of multiple genes needed for regeneration. We previously showed that two such genes, wg and Wnt6, are regulated by a single damage-responsive enhancer that becomes progressively inactivated via Polycomb-mediated silencing as discs mature (Harris et al., 2016). Here we explore the generality of this mechanism and identify additional damage-responsive, maturity-silenced (DRMS) enhancers, some near genes known to be required for regeneration such as Mmp1, and others near genes that we now show function in regeneration. Using a novel GAL4-independent ablation system we characterize two DRMS-associated genes, apontic (apt), which curtails regeneration and CG9752/asperous (aspr), which promotes it. This mechanism of suppressing regeneration by silencing damage-responsive enhancers at multiple loci can be partially overcome by reducing activity of the chromatin regulator extra sex combs (esc).
Data availability
Sequencing data have been deposited in GEO. Accession code: GSE140755. All other data generated or analyzed during this study are included in the manuscript and supporting files.
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Chromatin landscape changes of regenerating wing imaginal discsNCBI Gene Expression Omnibus, GSE140755.
Article and author information
Author details
Funding
National Institutes of Health (R35 GM122490)
- Iswar K Hariharan
American Cancer Society (RP-16238-06-COUN)
- Iswar K Hariharan
National Institutes of Health (R35 GM128851)
- Daniel J McKay
American Cancer Society (RSG-17-164-01-DDC)
- Daniel J McKay
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Hugo J Bellen, Baylor College of Medicine, United States
Version history
- Received: April 29, 2020
- Accepted: May 28, 2020
- Accepted Manuscript published: June 3, 2020 (version 1)
- Version of Record published: June 17, 2020 (version 2)
Copyright
© 2020, Harris 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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