SWItching on the transcriptional circuitry in melanoma

Abstract

Melanoma is an aggressive malignancy that is resistant to current therapy, and the most lethal of all human skin cancers. It is characterized by several genetic alterations that lead to changes in gene expression and tumorigenesis by triggering alterations in the normal transcriptional circuitry. Transformation and tumor progression are thought to be promoted by a complex interplay between the accumulation of genetic alterations and epigenetic changes. In this review, we discuss recent studies that have implicated SWI/SNF chromatin remodeling enzymes as epigenetic regulators of a transcriptional circuit that operates within the context the genetic alterations that frequently occur in melanoma.

Figure 1

(A) List of Mammalian SWI/SNF components including gene names and other commonly used designations. (B) Diverse SWI/SNF complexes containing either BRG1 or BRM and associated factors exist in mammalian cells. BRG1 and BRM are mutually exclusive. (C) Schematic comparison of BRG1 and BRM structure. The two ATPases are 70% identical, containing conserved as well as unique sequences. Stars represent lysine residues in BRM that can be post-translationally modified by acetylation.

Figure 2

Potential contribution of distinct SWI/SNF complexes containing either BRG1 or BRM in the regulation of different classes of MITF target genes.