To compare the function of endogenous ASCL1 in different neuroblastoma cell contexts, we have used CRISPR-mediated deletion to compare the effects of ASCL1 deletion in a MYCN-amplified and an ALK-driven neuroblastoma line, investigating cell proliferation and the genome-wide impact on gene expression, chromatin accessibility and on the regulation of the core regulatory circuit genes. Here, ASCL1 is linked to neuroblastoma.