Integrative epigenomic analysis in differentiated human primary bronchial epithelial cells exposed to cigarette smoke.

Cigarette smoke (CS) is one of the major risk factors for many pulmonary diseases, including chronic obstructive pulmonary disease (COPD) and lung cancer. The first line of defense for CS exposure is the bronchial epithelial cells. Elucidation of the epigenetic changes during CS exposure is key to gaining a mechanistic understanding into how mature and differentiated bronchial epithelial cells respond to CS. Therefore, we performed epigenomic profiling in conjunction with transcriptional profiling in well-differentiated human bronchial epithelial (HBE) cells cultured in air-liquid interface (ALI) exposed to the vapor phase of CS. The genome-wide enrichment of histone 3 lysine 27 acetylation was detected by chromatin immunoprecipitation followed by next generation sequencing (ChIP-Seq) in HBE cells and suggested the plausible binding of specific transcription factors related to CS exposure. Additionally, interrogation of ChIP-Seq data with gene expression profiling of HBE cells after CS exposure for different durations (3 hours, 2 days, 4 days) suggested that earlier epigenetic changes (3 hours after CS exposure) may be associated with later gene expression changes induced by CS exposure (4 days). The integration of epigenetics and gene expression data revealed signaling pathways related to CS-induced epigenetic changes in HBE cells that may identify novel regulatory pathways related to CS-induced COPD.