Show simple item record

dc.contributor.advisorHahn, Stevenen_US
dc.contributor.authorHan, Yanen_US
dc.date.accessioned2015-02-24T17:31:19Z
dc.date.submitted2014en_US
dc.identifier.otherHan_washington_0250E_13869.pdfen_US
dc.identifier.urihttp://hdl.handle.net/1773/27412
dc.descriptionThesis (Ph.D.)--University of Washington, 2014en_US
dc.description.abstractThe evolutionarily conserved transcription coactivator SAGA (Spt-Ada-Gcn5 Acetyltransferase) is a multi-subunit complex with a modular structure, which has several distinct activities that are used to regulate activator-dependent transcription. SAGA covalently modifies histones using its histone acetyltransferase (HAT) and deubiquitination (DUB) modules. It also directly regulates the formation of the transcription preinitiation complex (PIC) through direct interactions with both transcriptional activators and the TATA-box Binding Protein (TBP). Despite SAGA's important roles in regulating transcription, its overall architecture and structural organization of its modules remain unclear. The large size and complex subunit composition of SAGA make it difficult to study its structure using high-resolution approaches such as X-ray crystallography. Using an alternative approach, I combined chemical crosslinking with mass spectrometry (CXMS) to investigate the architecture of SAGA. In Chapter 2, I describe the results of my efforts using this approach, finding that the SAGA Taf and Taf-like subunits form a TFIID-like core complex at the center of SAGA that makes extensive interactions with all other SAGA modules. In Chapter 3, I show that the HAT and DUB modules are in close proximity, and the DUB module modestly stimulates HAT function. In Chapter 4, I describe the finding that SAGA-TBP binding involves a network of interactions between subunits Spt3, Spt8, Spt20, and Spt7, and the attempts I have made toward solving the crystal structure of Spt8 in complex with TBP. Finally, in Chapter 5, I combine all of the data and derive a model for the molecular architecture of the SAGA complex. My results provide new insight into SAGA function in gene regulation, its structural similarity with TFIID, and functional interactions between the SAGA modules.en_US
dc.format.mimetypeapplication/pdfen_US
dc.language.isoen_USen_US
dc.rightsCopyright is held by the individual authors.en_US
dc.subjectGene Regulation; Proteomics; SAGA; Transcriptionen_US
dc.subject.otherBiochemistryen_US
dc.subject.otherMolecular biologyen_US
dc.subject.otherbiological chemistryen_US
dc.titleArchitecture of the Saccharomyces cerevisiae SAGA transcription coactivator complexen_US
dc.typeThesisen_US
dc.embargo.termsRestrict to UW for 1 year -- then make Open Accessen_US
dc.embargo.lift2016-02-24T17:31:19Z


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record