Loss of Drosophila Ataxin-7, a SAGA subunit, reduces H2B ubiquitination and leads to neural and retinal degeneration.

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.

• Authors: Ryan D Mohan, George Dialynas, Vikki M Weake, Jianqi Liu, Skylar Martin-Brown, Laurence Florens, Michael P Washburn, Jerry L Workman, Susan M Abmayr
• Journal: Genes & development (Genes Dev) Vol. 28 Issue 3 Pg. 259-72 (Feb 01 2014) ISSN: 1549-5477 [Electronic] United States
• PMID: 24493646 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• ATXN7 protein, human
• Ataxin-7
• Histones
• Multiprotein Complexes
• Nerve Tissue Proteins
• Ubiquitin-Specific Proteases

Topics

• Amino Acid Sequence
• Animals
• Ataxin-7
• Drosophila melanogaster (enzymology, genetics, metabolism)
• HeLa Cells
• Histones (metabolism)
• Humans
• Longevity (genetics)
• Models, Molecular
• Molecular Sequence Data
• Multiprotein Complexes (genetics)
• Nerve Tissue Proteins (chemistry, deficiency, genetics, metabolism)
• Neurons (pathology)
• Promoter Regions, Genetic (genetics)
• Protein Structure, Quaternary
• Retina (pathology)
• Sequence Alignment
• Ubiquitin-Specific Proteases (genetics, metabolism)
• Ubiquitination