FIGURE 6.

Proteasome inhibitors reshape the chromatin landscape in MM by decreasing H3K27 acetylation at oncogenic promoters and super-enhancers. This epigenetic silencing is mediated by HDAC3, which accumulates at defined genomic sites following proteasome inhibition. The ubiquitin ligase SIAH2 facilitates the removal of HDAC3 from associated promoters and enhancers in the absence of treatment, either through direct degradation (shown) or through removal of a recruiting factor. MM, multiple myeloma; Co-rep, corepressor; TF, transcription factor; Ub, ubiquitin.