title: Cigarette smoke induces distinct histone modifications in lung cells: implications for the pathogenesis of COPD and lung cancer.
abstract: Cigarette smoke (CS)-mediated oxidative stress induces several signaling cascades, including kinases, which results in chromatin modifications (histone acetylation/deacetylation and histone methylation/demethylation). We have previously reported that CS induces chromatin remodeling in pro-inflammatory gene promoters; however, the underlying site-specific histone marks formed in histones H3 and H4 during CS exposure in lungs in vivo and in lung cells in vitro, which can either drive gene expression or repression, are not known. We hypothesize that CS exposure in mouse and human bronchial epithelial cells (H292) can cause site-specific posttranslational histone modifications (PTMs) that may play an important role in the pathogenesis of CS-induced chronic lung diseases. We used a bottom-up mass spectrometry approach to identify some potentially novel histone marks, including acetylation, monomethylation, and dimethylation, in specific lysine and arginine residues of histones H3 and H4 in mouse lungs and H292 cells. We found that CS-induced distinct posttranslational histone modification patterns in histone H3 and histone H4 in lung cells, which may be considered as usable biomarkers for CS-induced chronic lung diseases. These identified histone marks (histone H3 and histone H4) may play an important role in the epigenetic state during the pathogenesis of smoking-induced chronic lung diseases, such as chronic obstructive pulmonary disease and lung cancer.
authors.affiliation: Department of Environmental Medicine, †Lung Biology and Disease Program, University of Rochester Medical Center , Rochester, New York 14642, United States.
authors.forename: Isaac K
authors.initials: IK
authors.lastname: Sundar
authors.forename: Michael Z
authors.initials: MZ
authors.lastname: Nevid
authors.forename: Alan E
authors.initials: AE
authors.lastname: Friedman
authors.forename: Irfan
authors.initials: I
authors.lastname: Rahman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002853:Chromatography, Liquid; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008175:Lung Neoplasms / Q000209:etiology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana
chemical_list: D006657:Histones; D012906:Smoke