Leo1 deletion reveals Set1-dependent transcription activation

Histone H3 lysine 4 methylation is closely associated with gene expression, yet the instructive roles remain incompletely understood. In Saccharomyces cerevisiae, deletion of the Paf1C subunit Leo1 alters transcription without disrupting global H3K4 methylation levels or genome-wide distribution. Under these conditions, a subset of genes involved in sterol transport becomes highly induced and acquires de novo H3K4me3 at promoter-proximal regions. This transcriptional activation is abolished in leo1? set1? cells and restored by reintroduction of SET1, indicating that Set1-mediated H3K4me3 is required for their expression. The induced genes also exhibit enhanced sterol uptake, indicating physiological relevance. Importantly, these effects are specific to Leo1 deficiency and are not observed in mutants lacking other Paf1C components. Our findings define a native chromatin context in which H3K4me3 directly promotes gene activation, providing in vivo evidence for the instructive role of this histone modification. Overall design: Sample number (1-8): We performed RNA-seq with WT(1,2), leo1?(3,4), leo1?set1?(5.6), and paf1?(7,8) strains. Experiments were performed in duplicates.