Transcriptional profile and chromatin accessibility in zebrafish melanocytes and melanoma tumors

Abstract

Transcriptional and epigenetic characterization of melanocytes and melanoma cells isolated from their in vivo context promises to unveil key differences between these developmentally related normal and cancer cell populations. We therefore engineered an enhanced Danio rerio (zebrafish) melanoma model with fluorescently labeled melanocytes to allow for isolation of normal (wild type) and premalignant (BRAF^V600E-mutant) populations for comparison to fully transformed BRAF^V600E-mutant, p53 loss-of-function melanoma cells. Using fluorescence-activated cell sorting to isolate these populations, we performed high-quality RNA- and ATAC-seq on sorted zebrafish melanocytes vs. melanoma cells, which we provide as a resource here. Melanocytes had consistent transcriptional and accessibility profiles, as did melanoma cells. Comparing melanocytes and melanoma, we note 4128 differentially expressed genes and 56,936 differentially accessible regions with overall gene expression profiles analogous to human melanocytes and the pigmentation melanoma subtype. Combining the RNA- and ATAC-seq data surprisingly revealed that increased chromatin accessibility did not always correspond with increased gene expression, suggesting that though there is widespread dysregulation in chromatin accessibility in melanoma, there is a potentially more refined gene expression program driving cancerous melanoma. These data serve as a resource to identify candidate regulators of the normal vs. diseased states in a genetically controlled in vivo context.