Contributions of tumor suppressors to the epigenetic regulation of aging cells

Abstract

Epigenetics refers to the initiation and maintenance of heritable patterns of gene expression and function without changes in the primary DNA sequence. Covalent modifications of histones and DNA methylation are the most common epigenetic modifications that influence the activity of various growth stimulatory and inhibitory genes. Cellular senescence might be viewed as a state when the balance of gene activity is skewed in the favour of growth inhibitory genes. By virtue of its influence on gene activity, the epigenetic state of chromatin profoundly regulates the establishment and perpetuation of senescence. Chromatin remodelling complexes such as histone acetyl transferases and histone deacetylases are active players in engineering the epigenetic landscape that leads to senescence induction. A variety of tumor suppressors are important components of various chromatin remodelling complexes and effect their growth inhibitory activity by bringing chromatin modifying proteins to DNA. In this chapter we discuss how major tumor suppressor proteins like p53, p16, PTEN, and ING engineer a change in the epigenome and enforce the senescent phenotype, mainly by regulating the state of facultative euchromatin.