Fig. 2.

Suppression of cryptic intragenic transcripts by H3K36me3. Both the yeast Set2 and the mammalian SETD2 bind the elongating RNAPII and decorate the gene body regions with H3K36me3. In yeast (a), the H3K36me3 recruits the Rpd3S histone deacetylase complex to deacetylate the transcribed body regions to suppress spurious intragenic transcripts. Unlike yeast, the mammalian cells (b) employ different H3K36me3 ‘readers’, a de novo methyltransferase DNMT3B and the MRG15–KDM5B complex, to methylate DNA and remove H3K4me3, respectively, thus leading to inactivation of intragenic promoters; as well, SETD2 recruits the FACT complex to facilitate nucleosome structure recovery after RNAPII passage, thus preventing RNAPII entry into the intragenic promoters