Figure 8From: Exploiting gene deletion fitness effects in yeast to understand the modular architecture of protein complexes under different growth conditionsProposed model for the regulation of histone trimethylation by COMPASS through the recruitment of the attachment protein Doa4. The COMPASS methyltransferase protein complex methylates lysine 4 at histone H3 (H3-K4), regulated by ubiquitination of lysine 123 at histone H2B (H2B-K123) [32–35]. H3-K4 can be mono-, di- and tri-methylated and COMPASS is required for all three levels of methylation, while only tri-methylated H3-K4 leads to the activation of gene transcription [39, 40]. The two COMPASS components Spp1 and Bre2 are required for tri-methylation activity of the complex [40], but both belong to the core of COMPASS (shown in blue) and are present in all isoforms of the complex. The attachment protein Swd2 (orange) mediates the cross-talk between H2B-K123 monoubiquitination and H3-K4 di- and trimethylation [41]. Some isoforms of COMPASS contain the ubiquitin hydrolase Doa4 (magenta) as an attachment, and we thus propose that the addition of the third methyl group (green) to di-methylated H3-K4 by COMPASS is regulated by the recruitment of Doa4 to the complex. Removal of ubiquitin (purple) from H2B-K123 by Doa4 (indicated with scissors) would disrupt the association of Swd2 (orange) with chromatin (histones shown in grey with a black DNA string wrapped around), inhibiting H3-K4 trimethylation.Back to article page