The epigenomic landscape of multiple myeloma (MM)

NAISS 2023/22-621


NAISS Small Compute

Principal Investigator:

Antonia Kalushkova


Uppsala universitet

Start Date:


End Date:


Primary Classification:

30108: Cell and Molecular Biology




We have previously reported on the importance of gene targeting by the Polycomb repressor complex 2 (PRC2) for the pathophysiology of multiple myeloma (MM) (Kalushkova et al. 2010; Agarwal et al. 2016; Alzrigat et al. 2017). This involved the generation of a ChIP-seq profile of Polycomb targeting as defined by H3K27me3 in primary MM cells and normal counterpart plasma cells from age-matched donors (Agarwal et al. 2016). Further analysis of the data now indicates that aberrant H3K27me3 targeting might extend further from genes to distal putative regulatory regions. Polycomb proteins are known to regulate nuclear organization and PRC2 has been shown to participate in the long-range contacts between poised enhancers, marked by H3K4me1 and H3K27me3, and the target genes in ESCs. Upon differentiation, these poised enhancers exchange H3K27me3 by H3K27ac, becoming active in regulating their target genes (Cruz-Molina, Respuela et al. 2017). This prompts us to now define active enhancers in the normal counterpart in order to evaluate the possible decommissioning of these in the transformation to MM. This project is a continuation of project b2011152.