Yeast Sgf73/Ataxin-7 serves to anchor the deubiquitination module into both SAGA and Slik(SALSA) HAT complexes

Kenneth K Lee,Laurence Florens,Selene K Swanson,Jerry L Workman,Michael P Washburn

doi:10.1186/1756-8935-2-2

Kenneth K Lee, Laurence Florens + Show 3 more

Open Access

https://doi.org/10.1186/1756-8935-2-2

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Abstract

Spinocerebellar ataxia (SCA) is a physically devastating, genetically inherited disorder characterized by abnormal brain function that results in the progressive loss of the ability to coordinate movements. There are many types of SCAs as there are various gene mutations that can cause this disease. SCA types 1–3, 6–10, 12, and 17 result from a trinucleotide repeat expansion in the DNA-coding sequence. Intriguingly, recent work has demonstrated that increased trinucleotde expansions in the SCA7 gene result in defect in the function of the SAGA histone acetyltransferase complex. The SCA7 gene encodes a subunit of the SAGA complex. This subunit is conserved in yeast as the SGF73 gene. We demonstrate that Sgf73 is required to recruit the histone deubiquitination module into both SAGA and the related SliK(SALSA) complex, and to maintain levels of histone ubiquitination, which is necessary for regulation of transcription at a number of genes.

Highlights

Misregulation of transcription is a hallmark of a number of human diseases ranging from diverse classes of cancers to neurodegenerative diseases
Yeast Ataxin-7 is required to anchor the histone deubiquitination module into SAGA Our previous work, along with the work of others, has identified the core deubiquitination module with the SAGA/SLiK(SALSA) complex to be composed of Ubp8, Sgf11 and Sus1 [13,14,15]
Using TAP-tag purification followed by MudPit analysis we found that Ubp8 was only associated with the other core deubiquitination module members, Sgf11 and Sus1, upon the deletion of SGF73 (Figure 2A)

Summary

Introduction

Misregulation of transcription is a hallmark of a number of human diseases ranging from diverse classes of cancers to neurodegenerative diseases. Many transcriptional coactivator complexes possess intrinsic enzymatic activities that allow for access to DNA for transcription Chromatin remodeling complexes, such as ATPases, are a type of transcriptional coactivator complex that move nucleosomes, while histone acetyltransferases and histone methyltransferases are examples of complexes that modify histones post-translationally. Identified over 40 years ago, histone acetylation has become a model for understanding the role of histone modifications in modulating chromatin structure [4] To this end, the histone acetyltransferase Gcn and its associated complexes have been shown to regulate the transcription of up to 10% of genes in yeast [5].

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