Common differentiating agents facilitate transcriptional reprogramming by bromodomain inhibition

Dimethyl sulfoxide (DMSO) and hexamethylene bisacetamide (HMBA) are biologically active molecules that have shown clinical efficacy in cancer and inflammation, though their therapeutic application has been limited, partly because their mechanism of action is unknown. We demonstrate that DMSO and HMBA facilitate rapid transcriptional reprogramming via competitive inhibition of bromodomain-containing proteins. These results identify novel therapeutic avenues and provide context to over 50 years of biomedical research with these agents.

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