Structure-function studies of Jhd2, a histone H3K4 demethylase
Histone lysine (K) methylation is a dynamic process that plays an important role in regulating chromatin structure and gene expression. This study has identified Jhd2, a JmjC domain-containing protein, as an H3K4-specific demethylase in budding yeast. In addition, I show that Jhd2 has intrinsic activity to remove all three states of H3K4 methylation in vivo, and can dynamically associate with chromatin to modulate H3K4 methylation levels on both active and repressed genes and in the subtelomeric regions. I also provide evidence that the interaction between the JmjN and JmjC domains in Jhd2 is important for its protein stability, and Not4 (an E3 ubiquitin ligase) monitors the structural integrity of this inter-domain interaction to maintain the overall protein levels of Jhd2. Moreover, I find that the PHD finger of Jhd2 is important for its chromatin association in vivo by binding to the N-terminal region of H2A, suggesting a novel docking site on chromatin for Jhd2. In summary, this study has revealed important insights into the function and regulation of the H3K4 demethylase Jhd2.