Figure 8.

Model for Set1- and Set2-mediated choice of pA site. In wild-type cells, Set1 and Set2 mediate occupancy of histone H3K4me1 and H3K36me3 around pA sites. Methylation of histone H3K4 and H3K36 increases acetylation of nucleosomes, and assures an open chromatin structure, which allows RNAP II transcription to proceed to a downstream pA site (pA2), and production of long mRNA isoforms. Depletion of Set1 leads to loss of histone H3 and H4, reduction of histone H3K36me3, as well as increased phosphorylation of the RNAP II CTD Ser2 near pA1 site, resulting in recruitment of cleavage/polyadenylation factors. Loss of Set2 results in decreased nucleosome (Nuc) occupancy and histone H3K4me1 levels near the pA1 site which in turn enhances recruitment of the 3′ end processing complex.