Epigenetic Control of Gene Expression in the Lung

Abstract

Epigenetics is traditionally defined as the study of heritable changes in gene expression caused by mechanisms other than changes in the underlying DNA sequence. There are three main classes of epigenetic marks-DNA methylation, modifications of histone tails, and noncoding RNAs-each of which may be influenced by the environment, diet, diseases, and ageing. Importantly, epigenetic marks have been shown to influence immune cell maturation and are associated with the risk of developing various forms of cancer, including lung cancer. Moreover, there is emerging evidence that these epigenetic marks affect gene expression in the lung and are associated with benign lung diseases, such as asthma, chronic obstructive pulmonary disease, and interstitial lung disease. Technological advances have made it feasible to study epigenetic marks in the lung, and it is anticipated that this knowledge will enhance our understanding of the dynamic biology in the lung and lead to the development of novel diagnostic and therapeutic approaches for our patients with lung disease.

Epigenetic modifications and p21-cyclin B1 nexus in anticancer effect of histone deacetylase inhibitors in combination with silibinin on non-small cell lung cancer cells

“…2,5,7,8 At the cellular level, these alterations deregulate key cellular processes, like transcriptional control, DNA repair and cell cycle progression, which can further be modulated by environmental stressors. 5,39 Thus, epigenetic modifications are considered very attractive targets for the development of therapeutic approaches.…”

“…[2][3][4][5] Epigenetic events are heritable, yet reversible, dynamic changes in the genome that can occur in response to the environment, diet, disease and aging; they manifest in the form of DNA methylation, modifications of histone tails and non-coding RNAs. [5][6][7][8] Among these epigenetic events, the silencing of tumor suppressor…”

“…The implications of such an effect are tremendous, given the fact that HDACs 1-3 play an essential role in survival and proliferation of cancer cells, 17,40 and their overexpression has been associated with locally advanced, de-differentiated and strongly proliferating lung tumors. 2,5,8,40 Combinatorial treatment of HDACi TSA or SAHA with silibinin, against NSCLC H1299 cells, which are relatively resistant to TSA treatment, 17 significantly augmented the cytotoxic effects of the single agents. The synergistic cytotoxic effects of the combinations were also associated with increased pro-apoptotic effect.…”

Cigarette smoking induces small airway epithelial epigenetic changes with corresponding modulation of gene expression

“…Hypermethylation of CpG islands around gene promoters is generally correlated with gene silencing, whereas hypomethylation usually is associated with active gene transcription (4,5). Recent evidence suggests that the epigenome is affected by, and can rapidly respond to, external stimuli such as diet and environment (6 -25).…”

Asthma, environment and epigenetic

“…Epigenetik mekanizmalar ile regüle edilen astım ile ilişkili pek çok gen olduğu bilinmektedir. Gestasyonel dönemde Th2 fenotipine dönüşümde görülen hipermetilasyon allerjik hava yolu hastalıkları riskini artırmaktadır (18). Yaşlanmada DNA metilasyonu ve gen ekspresyonunda değişiklik-lere yol açabilir (19).…”