Proteasome inhibition silences oncogenic transcripts in multiple myeloma through HDAC3-mediated DNA condensation and gene relocation [CUT&RUN]

This study provides a genome-wide map of changes in degradative ubiquitination in response to proteasome inhibition in the multiple myeloma cell line MM.1S. Following proteasome inhibition with lactacystin, CUT and RUN assays were carried out to determine the genomic locations of ubiquitin in multiple myeloma cells stably expressing a flagged version of ubiquitin (MM.1S-3XFlag Ubiquitin cells). In addition, we report the DNA binding locations of the transcription factor c-MYC in basal conditions in MM.1S parental cells. Multiple myeloma cells MM.1S were treated for three hours with the synthetic proteasome inhibitor lactacystin and compared to DMSO control-treated cells in CUT & RUN experiments. We performed sequencing for degradative ubiquitination marks (3XFlag-ubiquitin) and the transcription factor c-MYC.