Specific Lysine Sites in Histone H3 Contribute To Spurious Transcription

Abstract

Transcriptional co‐factors including histone modifying enzymes regulate gene expression at both initiation and elongation stages of transcription. Recent studies demonstrate that Set2‐catalyzed histone H3K36 methylation serves as a signal for recruitment of histone deacetylase Rpd3 Small complex that decreases histone acetylation in coding regions and inhibits aberrant initiation of transcription from cryptic promoters within the coding region of certain genes. In this study, we investigated the possible roles of individual lysine sites in histones H3 and H4 in spurious transcription initiation by Northern blotting, chromatin immunoprecipitation and quantitative RT‐PCR. Our results indicate that H3K4 methylation, H3K14 and H3K23 acetylation specifically contribute to aberrant transcription initiation in the absence of Set2. H3K4 mutation synergistically enhances the suppression of cryptic transcription initiation by H3K14 and H3K23 mutations in set2 deletion. In addition, the functions of these three lysine sites in H3 in transcription initiation are regulated by a number of proteins including Ccr4‐Not complex, Set1 and Spt3 that participate in regulation of H3K4 methylation and histone H3 acetylation, suggesting a complex regulating network exists in cryptic transcription initiation. Our study reveals new roles for these three histone lysines in H3.