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Role Of The Gcn5 Histone Acetyltransferase In Spinocerebellar Ataxia Type 7 And In Immature Neurons, Yi Chun Chen
Role Of The Gcn5 Histone Acetyltransferase In Spinocerebellar Ataxia Type 7 And In Immature Neurons, Yi Chun Chen
Dissertations & Theses (Open Access)
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. …
Regulation Of Set1-Mediated Methylation Of Dam1, John A. Latham
Regulation Of Set1-Mediated Methylation Of Dam1, John A. Latham
Dissertations & Theses (Open Access)
Eukaryotic genomes exist within a dynamic structure named chromatin in which DNA is wrapped around an octamer of histones forming the nucleosome. Histones are modified by a range of posttranslational modifications including methylation, phosphorylation, and ubiquitination, which are integral to a range of DNA-templated processes including transcriptional regulation. A hallmark for transcriptional activity is methylation of histone H3 on lysine (K) 4 within active gene promoters. In S. cerevisiae, H3K4 methylation is mediated by Set1 within the COMPASS complex. Methylation requires prior ubiquitination of histone H2BK123 by the E2-E3 ligases Rad6 and Bre1, as well as the Paf1 transcriptional …