Chromatin 'resetting' during transcription elongation: a central role for methylated H3K36

Abstract

A number of events must occur to preserve the integrity of the chromatin template during gene transcription. A study in this issue reveals a novel mechanism whereby chromatin remodelers are recruited to histone modifications within gene bodies to prevent aberrant histone exchange during transcriptional elongation.

Figure 1. Set2 and histone H3K36 methylation safeguard transcription elongation

(a) Set2 interacts with RNAPII to methylate H3K36 across gene bodies. (b) In the absence of Set2, increased histone acetylation is detected across ORFs along with an accumulation of transcripts that arise from intragenic cryptic promoters. (c) The chromodomain of Eaf3 binds to methylated H3K36 and recruits the Rpd3C(S) HDAC complex to deacetylate histones in the 3′ ends of ORFs, which effectively suppresses the expression of transcripts from cryptic promoters. (d) Set2-mediated methylation of H3K36 blocks association of the Asf1 chaperone to prevent the exchange of pre-acetylated histones over the 3′ ends of ORFs, thereby suppressing cryptic transcription. (e) The PWWP domain within the Ioc4 subunit of Isw1b chromatin remodeling complex binds to methylated H3K36, and recruits the complex to the coding regions of genes undergoing transcription. Isw1b, along with Chd1, prevent the exchange of pre-acetylated histones over ORFs thereby suppressing the expression of transcripts from cryptic promoters.