title: Epigenetic control of cellular senescence in disease: opportunities for therapeutic intervention.
abstract: Understanding how senescence is established and maintained is an important area of study both for normal cell physiology and in tumourigenesis. Modifications to N-terminal tails of histone proteins, which can lead to chromatin remodelling, appear to be key to the regulation of the senescence phenotype. Epigenetic mechanisms such as modification of histone proteins have been shown to be sufficient to regulate gene expression levels and specific gene promoters can become epigenetically altered at senescence. This suggests that epigenetic mechanisms are important in senescence and further suggests epigenetic deregulation could play an important role in the bypass of senescence and the acquisition of a tumourigenic phenotype. Tumour suppressor proteins and cellular senescence are intimately linked and such proteins are now known to regulate gene expression through chromatin remodelling, again suggesting a link between chromatin modification and cellular senescence. Telomere dynamics and the expression of the telomerase genes are also both implicitly linked to senescence and tumourigenesis, and epigenetic deregulation of the telomerase gene promoters has been identified as a possible mechanism for the activation of telomere maintenance mechanisms in cancer. Recent studies have also suggested that epigenetic deregulation in stem cells could play an important role in carcinogenesis, and new models have been suggested for the attainment of tumourigenesis and bypass of senescence. Overall, proper regulation of the chromatin environment is suggested to have an important role in the senescence pathway, such that its deregulation could lead to tumourigenesis.
authors.affiliation: Centre for Oncology and Applied Pharmacology, University of Glasgow, Cancer Research UK Beatson Laboratories, Bearsden, Glasgow, G61 1BD, UK.
authors.forename: Stuart P
authors.initials: SP
authors.lastname: Atkinson
authors.forename: W Nicol
authors.initials: WN
authors.lastname: Keith
mesh_terms: D000818:Animals; D016922:Cellular Senescence / Q000502:physiology*; D002843:Chromatin / Q000235:genetics / Q000502:physiology*; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000502:physiology*
chemical_list: D002843:Chromatin; D006657:Histones; D025521:Tumor Suppressor Proteins