Interplay between genome organization and epigenomic alterations of pericentromeric DNA in cancer

Abstract

In eukaryotic genome biology, the genomic organization inside the three-dimensional (3D) nucleus is highly complex, and whether this organization governs gene expression is poorly understood. Nuclear lamina (NL) is a filamentous meshwork of proteins present at the lining of inner nuclear membrane that serves as an anchoring platform for genome organization. Large chromatin domains termed as lamina-associated domains (LADs), play a major role in silencing genes at the nuclear periphery. The interaction of the NL and genome is dynamic and stochastic. Furthermore, many genes change their positions during developmental processes or under disease conditions such as cancer, to activate certain sorts of genes and/or silence others. Pericentromeric heterochromatin (PCH) is mostly in the silenced region within the genome, which localizes at the nuclear periphery. Studies show that several genes located at the PCH are aberrantly expressed in cancer. The interesting question is that despite being localized in the pericentromeric region, how these genes still manage to overcome pericentromeric repression. Although epigenetic mechanisms control the expression of the pericentromeric region, recent studies about genome organization and genome-nuclear lamina interaction have shed light on a new aspect of pericentromeric gene regulation through a complex and coordinated interplay between epigenomic remodeling and genomic organization in cancer.

Keywords: Cancer; Epigenetics; Gene regulation; Genome organization; Heterochromatin; LADs; Pericentromere.