Transcription Elongation Medicated by the Chromatin Functions of Nap1

Del Rosario, Brian Cruz, Department of Microbiology, University of Virginia
Pemberton, Lucy, Department of Microbiology, University of Virginia
Rekosh, David, Department of Microbiology, University of Virginia
Beyer, Ann, Department of Microbiology, University of Virginia
Macara, Ian, Department of Microbiology, University of Virginia
Grant, Patrick, Department of Biochemistry and Molecular Genetics, University of Virginia

The process of chromatin remodeling is mediated by several factors including histone chaperones, ATP-dependent remodeling factors, and histone modifying enzymes. The orchestrated actions of these factors are central to regulating processes requiring access to the DNA fiber. We demonstrated for the first time that the conserved Saccharromyces cerevisiae histone chaperone Nap1 was associated with chromatin and has a role in RNAP II mediated transcription elongation. Chromatin remodeling is essential to the regulation of transcription elongation. During this phase of transcription, the coordinated displacement and reconstitution of nucleosomes is critical for polymerase processivity. We demonstrated that Nap1 regulated transcription of PHO5 with the net function of Nap1 being to facilitate nucleosome reassembly during transcription elongation. To further our understanding of this histone chaperone in transcription elongation, factors that regulate the function of Nap1 in this process were also identified. One factor investigated is the essential mRNA export and TREX complex component, Yra1. Nap1 interacted directly with Yra1 and genetically with other TREX components and the mRNA export factor Mex67. Additionally the recruitment of Nap1 to the coding region of actively transcribed genes was Yra1 dependent and its recruitment to promoters was TREX independent. These observations suggest that Nap1 functions provide a novel connection between chromatin assembly and mRNP biogenesis during transcription elongation. Additionally, since Nap1 histone chaperone activity likely occurs in concert with other chromatin remodeling factors during transcription elongation, several factors whose functions overlap those of Nap1 were identified using a genetic approach. It was found that Nap1 activities were important with those of histone chaperones, ATP-dependent chromatin remodeling enzymes, and histone modifying 3 enzymes. Importantly, the NAP1 genetic interaction with these factors not only supports a role for Nap1 in transcription elongation but also other chromatin based processes like DNA damage repair. Collectively, these studies also point to potential regulatory mechanisms that place Nap1 in the center of processes essential for cell development.

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PHD (Doctor of Philosophy)
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