SPECIFIC RESIDUES WITHIN HISTONE H2B REGULATE YEAST GENE EXPRESSION AND SILENCING, HISTONE H3 METHYLATION AND THE RESPONSE TO DNA DAMAGE
Kyriss, McKenna Nelson
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The histone proteins H3 and H4 have been extensively studied and are known to play well characterized roles in the regulation of yeast gene expression, silencing and the response to DNA damage. In contrast, relatively little is known about the functions of histones H2A and H2B in these processes. We have analyzed several histone H2B residues within the globular core domain of the nucleosome and the previously described histone H2B Repression (HBR) domain to better understand their roles in regulating these processes in yeast. We have found that yeast histone H2B residues K49, R102 and K111 are important for regulating the response to UV irradiation, and that H2B R102 and K111 have opposing effects on yeast gene silencing. Our analyses of the HBR domain have revealed that deletion of this domain causes an increase in the accumulation of UV induced damage within certain genomic loci, and that deletion of the HBR domain may reduce nucleotide excision repair by decreasing binding of yeast SWI/SNF chromatin remodeling complex. Additionally, we have found that deletion or mutation of this domain causes histone H2B depletion at numerous loci throughout the yeast genome, abolishes trimethylation of histone H3 lysine 4, and perturbs telomeric, mating type and ribosomal DNA silencing. Taken together, the work described in this dissertation shows that histone H2B plays a significant role in regulation of many critical processes in yeast.