Chromatin Modification and Senescence: Linkage by Tumor Suppressors?

Abstract

Senescence was originally defined as a state associated with cell cycle arrest that occurs after cells have undergone an intrinsically limited number of divisions in vitro. Much evidence indicates that senescence occurs as a consequence of the internal stress signal generated from shortening telomeres on the ends of chromosomes. However, more recently, various forms of extrinsic stresses have been shown to induce a markedly similar senescent phenotype that includes changes in chromatin structure and gene expression. Chromatin structure is subject to many forms of modification that affect transcription, gene silencing, cell proliferation, and senescence, much of which involves imposition of an epigenetic histone code. Several genes in the p53, Rb, and ING (inhibitor of growth) pathways affect cell senescence and are capable of regulating gene expression through chromatin remodeling. This suggests that a link may exist between chromatin modification and cellular senescence through the activity of proteins typically defined as tumor suppressors.