RNA-seq investigation of 1 Mb regions flanking the putative CSC-regulated enhancers. (A) Genes induced in a 1Mb window around each CpG in A549 cells treated for 48 h or 2 weeks with 20 µg/ml CSC. RNA-seq data were obtained from three independent treatments of A549 cells with CSC. (B) RNA-seq data from TCGA NTL samples (n = 100, Supplementary Material, Table S6) was analyzed to examine whether genes identified in A were associated with smoking history. NS= non-smoker; >15 and <15 indicates smoking cessation more than or less than 15 years ago. Fold change values between NS and current smoker were 4.58 for AHRR, 2.91 for CYP1B1, -0.40 for ENTPD2 and 0.87 for NR4A3. (C) TCGA NTL lung samples were used to examine the correlation between DNA methylation and RNA expression (n = 28, Supplementary Material, Table S8).