H3K4 Methylation Dependent and Independent Chromatin Regulation by and in Budding Yeast.

Set1 and Jhd2 regulate the methylation state of histone H3 lysine-4 (H3K4me) through their opposing methyltransferase and demethylase activities in the budding yeast H3K4me associates with actively transcribed genes and, like both and themselves, is known to regulate gene expression diversely. It remains unclear, however, if Set1 and Jhd2 act solely through H3K4me. Relevantly, Set1 methylates lysine residues in the kinetochore protein Dam1 while genetic studies of the ortholog suggest the existence of non-H3K4 Set1 targets relevant to gene regulation. We interrogated genetic interactions of and with essential genes involved in varied aspects of the transcription cycle. Our findings implicate in genetic inhibition of the histone chaperone complexes Spt16-Pob3 (FACT) and Spt6-Spn1 This targeted screen also revealed that inhibits the Nrd1-Nab3-Sen1 (NNS) transcription termination complex. We find that while Jhd2's impact on these transcription regulatory complexes likely acts via H3K4me, Set1 governs the roles of FACT and NNS through opposing H3K4-dependent and -independent functions. We also identify diametrically opposing consequences for mutation of H3K4 to alanine or arginine, illuminating that caution must be taken in interpreting histone mutation studies. Unlike FACT and NNS, detailed genetic studies suggest an H3K4me-centric mode of Spt6-Spn1 regulation by and Chromatin immunoprecipitation and transcript quantification experiments show that Jhd2 opposes the positioning of a Spt6-deposited nucleosome near the transcription start site of , a Spt6-Spn1 regulated gene, leading to hyper-induction of In addition to confirming and extending an emerging role for Jhd2 in the control of nucleosome occupancy near transcription start sites, our findings suggest some of the chromatin regulatory functions of Set1 are independent of H3K4 methylation.