Figure 1.

Suppression of cryptic transcription by the H3K36 methylation pathway. (A) In yeast, the recruitment of Set2 depends on the state of CTD S2P on RNA Pol II. The Eaf3 subunit in the Rpd3S HDAC complex recognizes Set2-mediated H3K36me3 and recruits the complex to the gene bodies, effectively suppressing cryptic transcription. (B) In mammals, H3K36me3 is co-transcriptionally added by SETD2 and serves as a scaffold to recruit the DNMT3B DNA methyltransferase, KDM5B H3K4 demethylase, and FACT histone chaperone complex. These processes work together to repress cryptic transcription.