University of Texas Health Science Center at Houston
Role of The Gcn5 Histone Acetyltransferase In Spinocerebellar Ataxia Type 7 and In Immature Neurons
Abstract
dc:description.abstract<p>Spinocerebellar Ataxia type 7 (SCA7) is a neurodegenerative disease caused by expansion of a CAG repeat encoding a polyglutamine tract in ATXN7, a component of the SAGA histone acetyltransferase (HAT) complex. Previous studies provided conflicting evidence regarding the effects of polyQ-ATXN7 on the activity of Gcn5, the HAT catalytic subunit of SAGA. Here I showed that reducing Gcn5 expression accelerates both cerebellar and retinal degeneration in a mouse model of SCA7. Deletion of Gcn5 in Purkinje cells in mice expressing wild type Atxn7, however, causes only mild ataxia and does not lead to the early lethality observed in SCA7 mice. Reduced Gcn5 expression strongly enhances retinopathy in SCA7 mice, but does not affect the transcriptional targets of Atxn7, as expression of these genes is not further altered by Gcn5 depletion. These findings demonstrate that loss of Gcn5 functions can contribute to the time of onset and severity of SCA7 phenotypes, but suggest that non-transcriptional functions of SAGA may play a role in neurodegeneration in this disease.</p>
Degree
thesis:*- Name thesis:degree_name
- Doctor of Philosophy (PhD)
- Level thesis:degree_level
- Dissertation (PhD)
- Year dc:date.available
- 2011
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Chen, Yi Chun
- Contributors dc:contributor
-
- Sharon Y. R. Dent, Ph.D.
- Richard R. Behringer, Ph.D.
- Xiaobing Shi, Ph.D.
Subjects
dc:subject × 9Identifiers
dc:identifier.*- Repository record dc:identifier
- https://digitalcommons.library.tmc.edu/utgsbs_dissertations/208
- OAI identifier oai:identifier
- oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1237