Nickel-induced alterations to chromatin structure and function

Abstract

Nickel (Ni), a heavy metal is prevalent in the atmosphere due to both natural and anthropogenic activities. Ni is a carcinogen implicated in the development of lung and nasal cancers in humans. Furthermore, Ni exposure is associated with a number of chronic lung diseases in humans including asthma, chronic bronchitis, emphysema, pulmonary fibrosis, pulmonary edema and chronic obstructive pulmonary disease (COPD). While Ni compounds are weak mutagens, a number of studies have demonstrated the potential of Ni to alter the epigenome, suggesting epigenomic dysregulation as an important underlying cause for its pathogenicity. In the eukaryotic nucleus, the DNA is organized in a three-dimensional (3D) space through assembly of higher order chromatin structures. Such an organization is critically important for transcription and other biological activities. Accumulating evidence suggests that by negatively affecting various cellular regulatory processes, Ni could potentially affect chromatin organization. In this review, we discuss the role of Ni in altering the chromatin architecture, which potentially plays a major role in Ni pathogenicity.

Keywords: Bivalency; CTCF; Chromatin architecture; Epigenetics; H3K9me2; Heterochromatin; Nickel.