Two Distinct Repressive Mechanisms for Histone 3 Lysine 4 Methylation through Promoting 3′-End Antisense Transcription

摘要: Histone H3 di- and trimethylation on lysine 4 are major chromatin marks that correlate with active transcription. The influence of these modifications transcription itself is, however, poorly understood. We have investigated the roles H3K4 methylation in Saccharomyces cerevisiae by determining genome-wide expression-profiles mutants Set1 complex, COMPASS, lays down marks. Loss has virtually no effect steady-state or dynamically-changing mRNA levels. Combined loss tri- dimethylation results upregulation delays repression kinetics specific groups genes. COMPASS-repressed genes distinct patterns, enrichment H3K4me3 at 3′-end, indicating is coupled to 3′-end antisense Further analyses reveal mediated H3K4me3-dependent two ways. For a small group including PHO84, previously reported trans-effect requires transcript itself. majority genes, it process important factor for repression. Strand-specific qPCR various indicate this more prevalent mechanism COMPASS-mediated lay H3K4me2, which seems serve as actual repressive mark. Removal promoter also derepression sense renders insensitive additional SET1. observed COMPASS mimicked reduction global histone H4 levels, suggesting H3K4me2 linked establishment structure. These S. cerevisiae, non-redundant role repression, achieved through promotion achieve rather than effects mechanisms.