Developmental Control Throughout the Budding Yeast Life Cycle by Jhd2, a JARID family Histone H3 Lysine-4 Demethylase

Histone H3 lysine 4 methylation (H3K4me) is a well-studied chromatin modification that is associated with active transcription; however, its physiological roles are not well understood. The importance of maintaining proper H3K4 methylation dynamics is underlined by the fact that H3K4 methyl transferases and demethylases control the balance between pluripotency and differentiation across eukaryotes, and their misregulation is associated with oncogenesis in mammals. My research contributed to the conclusion that the budding yeast JARID1 family H3K4 demethylase, encoded by JHD2, is required during yeast gametogenesis (sporulation) to sustain the duration of global gene expression in opposition to developmentally programmed transcriptional quiescence. In accordance with this, Jhd2 contributes to gamete fitness.;To elucidate the underlying mechanisms of Jhd2 function during sporulation, I quantified mRNA transcript accumulation and mapped genome-wide nucleosome positioning using high resolution tiling microarrays over time courses, and carried out analysis of the H3K4me landscape by ChIP (chromatin immunoprecipitation) microarray. By integrating data analysis from these experiments, I determined that Jhd2 represses interfering non-coding transcription during post-meiotic stages of sporulation, and that this repression correlates with increased levels of protein-coding genes. I went on to characterize 3' NDRs by performing integrative analyses on nucleosome occupancy and mRNA transcript abundance microarray data sets, and found that both transcription and DNA-histone interactions influence 3' NDR structure.;Furthermore, I found that Jhd2 promotes expression of genes involved in mitochondrial function and positively regulates mitochondrial respiration during sporulation and germination. My studies support the idea that spores utilize a maternal load of cellular resources to drive the earliest stages of germination prior to commencement of de novo transcription.;Together these studies show that Jhd2/JARID1 plays important roles during development and differentiation in budding yeast, and genomic data sets support a model whereby Jhd2 regulates gene expression via modulating levels of gene-associated non-coding transcription.