Chromatin Landscape of Saccharomyces cerevisiae Acquiring H3K9 Methylation and Its Reader Molecule HP1

Histone H3 lysine 9 (H3K9) methylation and heterochromatin protein 1 (HP1) are well-conserved heterochromatin epigenomes and their reader molecules. However, the details of the importance of them in heterochromatin formation still remain unclear. One reason for this is system redundancy, as multiple HP1 family proteins exist, as well as HP1 itself serving as hubs for various effector factors. To overcome these issues, we took a synthetic biology approach and introduced H3K9 methylation catalyzed by mouse H3K9 methyltransferases and HP1s into budding yeast, Saccharomyces cerevisiae (S. cerevisiae) which doesn't have this system, and examined its impact on transcription and chromatin compaction. We observed that the mammalian H3K9 methyltransferase can induce genome-wide H3K9 di- and tri-methylation in the S. cerevisiae, mainly in the gene body region, and HP1 accumulates over the H3K9 methylated regions. The forced expression of H3K9 methyltransferase and HP1 had little impact on transcription. Furthermore, Hi-C-seq analysis revealed no significant effects on the chromatin 3D structure. These results suggest that although H3K9 methylation and the recruitment of HP1 play essential roles in the epigenetic regulation of heterochromatin, they alone are not sufficient to alter the higher-order chromatin structure, at least in the gene body regions in S. cerevisiae.