Cellular epigenetic stability and cancer

• Published in: Trends in genetics Vol. 28; no. 3; pp. 118 - 127
• Main Authors: Sarkies, Peter, Sale, Julian E.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01.03.2012; Elsevier
• Subjects: Animals; Biological and medical sciences; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; DNA; DNA methylation; DNA replication; Epigenesis, Genetic; epigenetics; Fundamental and applied biological sciences. Psychology; gene expression; Genetics of eukaryotes. Biological and molecular evolution; genome; histones; Histones - metabolism; Humans; Medical Education; Molecular and cellular biology; neoplasm cells; Neoplasms - genetics; non-coding RNA; post-translational modification; Protein Processing, Post-Translational; transcription (genetics); transcription factors; Transcription, Genetic; Epigenetics; Genetics; Stability; Malignant tumor; Cancer
• ISSN: 0168-9525
• DOI: 10.1016/j.tig.2011.11.005

When a cell divides, it must not only accurately duplicate its genome, but also restore its previous levels of gene expression. The information determining gene expression is often not directly encoded in the DNA and is hence termed ‘epigenetic’. The molecular basis of epigenetic memory remains a subject of intense debate, but is likely to arise from the collaboration of several mechanisms, including histone post-translational modifications, transcription factors, DNA methylation and noncoding RNAs. In this article, we look at how these mechanisms interact to generate robust epigenetic states. We then consider recent observations that mitotic inheritance of stable gene expression can be compromised by interruption of DNA replication. We discuss how these data may provide direct evidence for a central role for histone modifications in transcriptional memory and how they could potentially provide an explanation for the some of the widespread alterations in transcription seen in cancer cells.