Trans-Histone Crosstalk-Mediated Establishment of Mutually Exclusive H3K79 Methylation Zones [RNA-Seq]

ABSTRACT: Histone H3 lysine 79 (H3K79) methylation plays critical roles in various cellular processes, including development and DNA repair, potentially through modulation of chromatin structure and gene expression. Despite its importance, the genome-wide distribution patterns, mechanisms of establishment, and functional distinctions among its mono-, di-, and tri-methylated forms (H3K79me1, me2, and me3) remain largely unclear. Here, we generated genome-wide maps of H3K79me1, H3K79me2, and H3K79me3 using ChIP-seq and found that each methylation state is predominantly associated with a unique subset of genes, which we term state-specific H3K79 methylation zones. These zones are mutually exclusive and are stably maintained even during global transcriptional reprogramming. We further demonstrate that H2B ubiquitination mediated by the Rad6-Bre1 complex is essential for the integrity of these methylation zones. Specifically, deletion of RAD6 leads to the complete loss of the H3K79me3 zone and its conversion into an H3K79me1-enriched region. Interestingly, the H3K79me1 zone is also significantly diminished upon RAD6 deletion, indicating that H2B ubiquitination supports both the maintenance and establishment of specific methylation zones. Similar disruption of the H3K79me1 landscape is observed upon loss of H4K16 acetylation. Functionally, H3K79me1 and H3K79me3 appear to have opposing roles in transcriptional regulation as loss of H3K79 methyltransferase Dot1 results in transcriptional activation of genes within the H3K79me1 zone and repression of genes within the H3K79me3 zone. Together, our findings reveal that distinct H3K79 methylation states define specific and functionally divergent chromatin domains, whose establishment and maintenance depend on trans-histone crosstalk and contribute to opposing transcriptional outputs.

ORGANISM(S): Saccharomyces cerevisiae

PROVIDER: GSE310163 | GEO | 2026/03/12

REPOSITORIES: GEO