Interaction of SIR Mediated Chromatin Modification of Mono-Nucleosome and Varying Di-Nucleosome Constructs

Zhang, Angel

Undergraduate Honors Thesis

Interaction of SIR Mediated Chromatin Modification of Mono-Nucleosome and Varying Di-Nucleosome Constructs Public Deposited

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Citeable URL: https://scholar.colorado.edu/concern/undergraduate_honors_theses/fb494988g

Abstract

Post-translational modifications serve as a key regulator of gene expression providing the basis for cellular differentiation in organisms. Transcriptional activation and silencing of genes is mediated by the recruitment of highly specific protein complexes to target DNA sequences. Complexes that modify chromatin alter the structure and accessibility of chromatin to transcriptional machinery to regulate gene expression. The silent information regulator (SIR) complex is found in Saccharomyces cerevisiae and plays a key role in the silencing of mating-type loci. The functional mechanism of nucleosome/DNA binding and structure of individual SIR proteins is still poorly understood. Preliminary analysis of Sir 3 binding, has displayed that Sir 3 binds to wild-type nucleosome DNA with higher affinity than 147 bp mono-nucleosome and WT 227 mono-nucleosome structures. Additionally, Sir 3 binding of mono-nucleosome structures has shown that Sir 3 binds DNA sequences flanking the nucleosome core particle (NCP) in addition to direct binding of the NCP. Additionally, Sir 2/4 was determined to be capable of binding nucleosome DNA and nucleosome core particles with reduced affinity compared to Sir 3. Characterization and full functional analysis of individual SIR proteins will provide more mechanistic insight to the binding and formation of silent chromatin in S. cerevisiae as well as a broader understanding of sirtuins in general. Further investigation into the SIR complex will provide a molecular framework for the transcriptional silencing of genes in S. cerevisiae, and hopefully, higher eukaryotes.

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