Current perspectives on role of chromatin modifications and deacetylases in lung inflammation in COPD.
Chromatin modifications and epigenetic regulation are critical for sustained and abnormal inflammatory response seen in lungs of patients with chronic obstructive pulmonary disease (COPD) because the activities of enzymes that regulate these epigenetic modifications are altered in response to cigarette smoke. Cigarette smoke induces chromatin modifications and epigenetic changes by causing post-translational modifications of histone acetyltransferases, and histone/non-histone deacetylases (HDACs), such as HDAC2 and sirtuin 1 (SIRT1), which leads to chromatin remodeling. In this review, we discussed the current knowledge on cigarette smoke/oxidants-induced post-translational modifications of deacetylases (HDAC2 and SIRT1), disruption of HDAC2/SIRT1-RelA/p65 corepressor complex associated with acetylation of RelA/p65, and chromatin modifications (histone H3 phospho-acetylation) leading to sustained pro-inflammatory gene transcription. Knowledge on molecular mechanisms of epigenetic changes in abnormal lung inflammation will help in understanding the pathophysiology of COPD which may lead to the development of novel epigenetic therapies in the near future.
Rajendrasozhan
Saravanan
S
Department of Environmental Medicine, Lung Biology and Disease Program, University of Rochester Medical Center, Rochester, New York, USA.
Yao
Hongwei
H
Rahman
Irfan
I
D002843:Chromatin / Q000378:metabolism*; D044127:Epigenesis, Genetic; D056464:Histone Deacetylase 2 / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010766:Phosphorylation; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology* / Q000209:etiology / Q000235:genetics; D056564:Sirtuin 1 / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects
D002843:Chromatin; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases