global methylation patterns in idiopathic pulmonary fibrosis全球甲基化模式在特发性肺纤维化.pdfVIP

Global Methylation Patterns in Idiopathic Pulmonary Fibrosis 1 1 2 1 1 Einat I. Rabinovich , Maria G. Kapetanaki , Israel Steinfeld , Kevin F. Gibson , Kusum V. Pandit , 1 2,3 1 Guoying Yu , Zohar Yakhini , Naftali Kaminski * 1 Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania, United States of America, 2 Department of Computer Sciences, Technion – Israel Institute of Technology, Haifa, Israel, 3 Agilent Laboratories, Tel-Aviv, Israel Abstract Background: Idiopathic Pulmonary Fibrosis (IPF) is characterized by profound changes in the lung phenotype including excessive extracellular matrix deposition, myofibroblast foci, alveolar epithelial cell hyperplasia and extensive remodeling. The role of epigenetic changes in determining the lung phenotype in IPF is unknown. In this study we determine whether IPF lungs exhibit an altered global methylation profile. Methodology/Principal Findings: Immunoprecipitated methylated DNA from 12 IPF lungs, 10 lung adenocarcinomas and 10 normal histology lungs was hybridized to Agilent human CpG Islands Microarrays and data analysis was performed using BRB-Array Tools and DAVID Bioinformatics Resources software packages. Array results were validated using the EpiTYPER MassARRAY platform for 3 CpG islands. 625 CpG islands were differentially methylated between IPF and control lungs with an estimated False Discovery Rate less than 5%. The genes associated with the differentially methylated CpG islands are involved in regulation of apop