SUMOylation regulates daunorubicin-induced changes in the long-range interactions between NFKB2 promoter and distant genomic regions in HL-60 cells

SUMOylation, a post-translational modification of the ubiquitin family plays key roles in Acute Myeloid Leukemias response to therapies, in particular through the regulation of gene expression. We have found that the NFKB2 gene is rapidly induced by DNR in the HL-60 cell line and inhibition of SUMOylation limits is induction. To decipher how SUMOylation controls DNR-induced NFKB2 expression, we analyzed the dynamic of the 3D conformation of the NFKB2 gene using Circularized Chromosome Conformation Capture (4C). We found that the NFKB2 promoter interacts with four distal regions. DNR induced a loss of one of the interaction and the gain of a new interaction. Inhibition of SUMOylation with ML-792 did not affect the interactions between NFKB2 promoter and distal genomic regions. However, inhibition of SUMOylation prevented DNR-regulated changes in the 3D architecture of the locus. The 4C approaches was performed in 3 biological replictes in HL-60 after 2 hours of treatment with DMSO (mock), DNR (1µM), ML-792 (0,5µM) and the combination of ML-792 (0,5µM) and DNR (1µM). The NFKB2 gene promoter has been used as a viewpoint for the technique.