Loss of Drosophila Ataxin-7, a SAGA subunit, reduces H2B ubiquitination and leads to neural and retinal degeneration
- Ryan D. Mohan1,
- George Dialynas1,
- Vikki M. Weake2,
- Jianqi Liu1,
- Skylar Martin-Brown1,
- Laurence Florens1,
- Michael P. Washburn1,3,
- Jerry L. Workman1,5 and
- Susan M. Abmayr1,4,5
- 1Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA;
- 2Department of Biochemistry, Purdue University, West Lafayette, Indiana 47907, USA;
- 3Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, USA;
- 4Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA
Abstract
The Spt–Ada–Gcn5–acetyltransferase (SAGA) chromatin-modifying complex possesses acetyltransferase and deubiquitinase activities. Within this modular complex, Ataxin-7 anchors the deubiquitinase activity to the larger complex. Here we identified and characterized Drosophila Ataxin-7 and found that reduction of Ataxin-7 protein results in loss of components from the SAGA complex. In contrast to yeast, where loss of Ataxin-7 inactivates the deubiquitinase and results in increased H2B ubiquitination, loss of Ataxin-7 results in decreased H2B ubiquitination and H3K9 acetylation without affecting other histone marks. Interestingly, the effect on ubiquitination was conserved in human cells, suggesting a novel mechanism regulating histone deubiquitination in higher organisms. Consistent with this mechanism in vivo, we found that a recombinant deubiquitinase module is active in the absence of Ataxin-7 in vitro. When we examined the consequences of reduced Ataxin-7 in vivo, we found that flies exhibited pronounced neural and retinal degeneration, impaired movement, and early lethality.
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Footnotes
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↵5 Corresponding authors
E-mail jlw{at}stowers.org
E-mail sma{at}stowers.org
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Supplemental material is available for this article.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.225151.113.
Freely available online through the Genes & Development Open Access option.
- Received June 22, 2013.
- Accepted December 19, 2013.
This article, published in Genes & Development, is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.