Transcriptional dysregulation of BAHCC1 in melanoma [CUT&Tag]

Transcriptional addiction of cancer cells for Super-Enhancer (SE) associated genes has been proven through an extensive use of transcriptional inhibitors against specific co-activators toward which SE are esponentially dependent compared to canonical enhancers. However, each cancer type displays different sensitivity against this new class of drugs whose efficacy may vary according to their transcriptomic profile including the expression of enzymatic proteins able to confer intrinsic tolerance or resistance. Moreover, SE has been observed as well in healthy cells which point a realistic concern toward the specificity of transcriptional inhibitors and their side effects on healthy tissues. Therefore, we looked at SE-associated genes specific for cancer using melanoma as a model. Here, we identified BAHCC1 whose activity is higher in melanoma compare to other cancer types and normal tissues. BAHCC1 is a protein involved both in gene expression and genomic stability. To explore BAHCC1 role in gene expression, we performed functional studies in melanoma cells in basal conditions or upon BAHCC1 silencing. Strikingly, BAHCC1 regulates an E2F-dependent subset of genes together with SWI/SNF chromatin remodelling complex. Overall design: Cleavage Under Targets and Tagmentation (CUT&Tag) of BAHCC1 followed by deep sequencing