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The Saccharomyces cerevisiae Paf1 transcription elongation complex is connected to chromatin modification through the multifunctional Rtf1 subunit and the inositol polyphosphate signaling pathway

Warner, Marcie Helene (2009) The Saccharomyces cerevisiae Paf1 transcription elongation complex is connected to chromatin modification through the multifunctional Rtf1 subunit and the inositol polyphosphate signaling pathway. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Transcription in eukaryotes takes place in the context of a repressive chromatin template. Access to the DNA is facilitated by histone modifying enzymes and ATP-dependent chromatin remodeling complexes, which modify chromatin structure. The activities of chromatin modifying proteins are often coordinated by nonenzymatic accessory factors that interact with actively transcribing RNA Polymerase II (Pol II). One such factor is the Saccharomyces cerevisiae Paf1 transcription elongation complex. This complex, which is minimally composed of Paf1, Ctr9, Rtf1, Cdc73, and Leo1, physically interacts with Pol II and localizes to the coding regions of active genes.The Rtf1 subunit of the Paf1 complex performs several cotranscriptional functions: it facilitates recruitment of the chromatin remodeling enzyme Chd1, promotes covalent modification of specific lysine residues in histones H2B and H3, and mediates association of other Paf1 complex subunits. Using a collection of internal deletion mutations that remove 20 to 50 amino acid segments across the length of Rtf1, I demonstrated that Rtf1's known functions are mediated by nonoverlapping regions, implying that the multiple functions of this protein are not completely interrelated. Deletion of the regions of Rtf1 that are required for promoting histone modification or its association with active genes resulted in the strongest transcription-related phenotypes, which suggested that promoting cotranscriptional histone modification is a critical means by which Rtf1 exerts its effects on transcription. Detailed analysis of the region of Rtf1 required for histone modification determined that it is sufficient to promote Rtf1-dependent histone modifications and that this function is dependent on several highly conserved residues.Additionally, a screen for factors that become essential in the absence of Rtf1 uncovered mutations in the first two enzymes of the inositol polyphosphate (IP) signaling pathway: Plc1 and Arg82. The IP signaling pathway has been linked to the function of several chromatin remodeling complexes. I uncovered strong genetic interactions between Arg82, Paf1, and mutations in the SWI/SNF and INO80 chromatin remodeling complexes and demonstrated that the expression of several target genes was strongly impaired by mutations in these factors. Together, these data suggest that transcription elongation, IP signaling, and chromatin remodeling cooperate to coordinate proper gene expression.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Warner, Marcie Helenemaw37@pitt.eduMAW37
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairArndt, Karen Marndt@pitt.eduARNDT
Committee MemberSchwacha, Anthonyschwacha@pitt.eduSCHWACHA
Committee MemberChapman, Deborah Ldlc7@pitt.eduDLC7
Committee MemberLeuba, Sanford Hleuba@pitt.eduLEUBA
Committee MemberSaunders, Williamwsaund@pitt.eduWSAUND
Date: 29 January 2009
Date Type: Completion
Defense Date: 10 October 2008
Approval Date: 29 January 2009
Submission Date: 24 October 2008
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Biological Sciences
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: chromatin; histone modification; Paf1 complex; Rtf1; transcription
Other ID:, etd-10242008-161432
Date Deposited: 10 Nov 2011 20:03
Last Modified: 15 Nov 2016 13:50


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