Fig. 2.

The SRI and AID domain reciprocally regulate Set2 activity. A The SRI domain directly interacts with the pCTD of RNAPII. The emerging model is that this interaction not only recruits Set2 to gene bodies but that it also controls Set2 activity by alleviating the negative regulation of the AID on the activity of the SET domain. The Spn1-Spt6 (IWS1-SUPT6H in humans) complex, which directly associates with RNAPII, stimulates the interaction between the SRI domain and the pCTD, although how this works on the molecular level is unknown. B In absence of the SRI domain (or in genomic regions where there is no RNA-pCTD) Set2 is unable to trimethylated H3K36