Tracking Epigenetic Modification-Mediated Genome Organization

Spatiotemporal control of chromatin structure and dynamics at sub-kilobase to megabase scales is essential for genome function. Epigenetic modification plays important roles in transcriptional regulation. How histone marks regulate genome organization at different scales remain unclear. Here we introduce an EpiGo (Epigenetic perturbation induced Genome organization) system to modify hundreds of genomic loci with H3K9me3 spanning megabases on human chromosome 19 and simultaneously track their changes of genome organization. EpiGo-mediated H3K9me3 spreads more extensively in transcriptionally inactive regions than active regions. H3K9 trimethylation of active regions trigger local chromatin compaction without substantial gene silencing. H3K9 trimethylated loci or regions associate with HP1a condensates and adjacent loci with H3K9me3 coalesce over time. H3K9 trimethylation of inactive regions reshape local genome compartmentalization. These results reveal that H3K9me3 mediates local chromatin compaction or genome compartmentalization upon distinct transcriptional states. We introduce an EpiGo (Epigenetic perturbation induced Genome organization) system to modify hundreds of genomic loci with H3K9me3 spanning megabases on human chromosome 19 and simultaneously track their changes of genome organization.