Abstract

Eukaryotic cells can establish distinct heritable phenotypic states with epigenetic modifications. Histone H3K9 methylation (H3K9me) is a conserved epigenetic modification that is associated with transcriptional silencing and heterochromatin formation. The diverse functions of heterochromatin depend on the evolutionarily conserved HP1 family of proteins that recognize and bind to H3K9me nucleosomes. Schizosaccharomyces pombe (fission yeast) have two HP1 homologs, Swi6 and Chp2, which play indispensable roles in regulating heterochromatin structure. Swi6 simultaneously binds to H3K9me and oligomerizes, which enables the spreading of heterochromatin and transcriptional silencing. On the other hand, Chp2 binds to H3K9me and recruits the Nucleosome Remodeling and Deacetylase complex, SHREC, through interaction with the histone remodeler Mit1. The putative H3K9 demethylase Epe1 interacts with Swi6 while the histone deacetylase Clr3 is a part of SHREC, and Epe1 and Clr3 are shown to have opposing effects on nucleosome turnover and heterochromatin formation. Structural biology and in vitro biochemistry assays have revealed the interactions between these histone modification proteins involved in the heterochromatin formation, however, there has not yet been any in vivo measurement of the interaction between these proteins. Here, we use live-cell single-particle tracking (SPT) and super-resolution microscopy to investigate the in vivo dynamics and spatial organization of histone modification proteins. With nonparametric Bayesian analysis of SPT trajectories, we measure distinct biophysical mobility states and map these states to the potential in vivo biochemical role. We propose a new mechanism for histone modification proteins in which the heterochromatin site is the primary location for protein complex formation, and H3K9me is a required substrate for the interaction.

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