Epigenomics
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Idiopathic pulmonary fibrosis (IPF) is a complex lung disease of unknown etiology. Development of IPF is influenced by both genetic and environmental factors. ⋯ This review will begin with an introduction to the disease, followed by brief summaries of studies of gene expression in IPF and epigenetic marks associated with exposures relevant to IPF. The majority of the discussion will focus on epigenetic studies conducted so far in IPF, the limitations, challenges nd future directions in this field.
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Epigenetic mechanisms have long been associated with the regulation of gene-expression changes accompanying normal neuronal development and cellular differentiation; however, until recently these mechanisms were believed to be statically quiet in the adult brain. Behavioral neuroscientists have now begun to investigate these epigenetic mechanisms as potential regulators of gene-transcription changes in the CNS subserving synaptic plasticity and long-term memory (LTM) formation. Experimental evidence from learning and memory animal models has demonstrated that active chromatin remodeling occurs in terminally differentiated postmitotic neurons, suggesting that these molecular processes are indeed intimately involved in several stages of LTM formation, including consolidation, reconsolidation and extinction. ⋯ The present article examines how such learning-induced epigenetic changes contribute to LTM formation and influence behavior. In particular, this article is a survey of the specific epigenetic mechanisms that have been demonstrated to regulate gene expression for both transcription factors and growth factors in the CNS, which are critical for LTM formation and storage, as well as how aberrant epigenetic processing can contribute to psychological states such as schizophrenia and drug addiction. Together, the findings highlighted in this article support a novel role for epigenetic mechanisms in the adult CNS serving as potential key molecular regulators of gene-transcription changes necessary for LTM formation and adult behavior.
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Classical genetic studies established a link between Type 1 diabetes, a common childhood autoimmune disease and genes that encode MHC antigens and several immune-related determinants. The mechanisms by which these genes contribute to the initiation and perpetuation of Type 1 diabetes remain enigmatic. ⋯ In this article the implications of these and other epigenetic mechanisms including ncRNA-mediated gene regulation in the abrogation of autoimmune diabetes are discussed. Concerted efforts to decipher the epigenetics of Type 1 diabetes may provide novel perspectives on autoimmune diabetogenesis.
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Asthma is a chronic inflammatory disease of the airways. The causes of asthma and other inflammatory lung diseases are thought to be both environmental and heritable. Genetic studies do not adequately explain the heritability and susceptabilty to the disease, and recent evidence suggests that epigentic changes may underlie these processes. ⋯ In addition, alterations in histone acetyltransferase/deacetylase activities can be observed in the cells of patients with lung diseases such as severe asthma and chronic obstructive pulmonary disease, and are often linked to smoking. Drugs such as glucocorticoids, which are used to control inflammation, are dependent on histone deacetylase activity, which may be important in patients with severe asthma and chronic obstructive pulmonary disease who do not respond well to glucocorticoid therapy. Future work targeting specific histone acetyltransferases/deacetylases or (de)methylases may prove to be effective future anti-inflammatory treatments for patients with treatment-unresponsive asthma.