Genomic DNA from five patients with diffuse cutaneous SSc was isolated from PBS- and DZNep (5 μM)-treated dermal fibroblasts, and subsequently, bisulfite converted using an EZ DNA Methylation kit (Zymo Research). Genome-wide DNA methylation was evaluated using the Illumina Infinium MethylationEPIC BeadChip Array, which allows measuring DNA methylation levels in over 850,000 CpG sites across the genome, and covers 27,364 annotated genes. The array also covers enhancers, regions of open chromatin identified by ENCODE project, DNase hypersensitive sites, and miRNA promoter regions. Analysis was performed using the Illumina GenomeStudio platform as described (28 (link)). The average level of DNA methylation (β) on each CpG site was compared between PBS- and DZNep-treated samples. Differentially methylated CpG sites were defined as those with a differential methylation score ≥|22| (equivalent to P value of less than 0.01 after adjusting for multiple testing) and a mean methylation difference greater than 10% between the two groups. Differentially methylated genes were analyzed for Gene Ontology (GO), network, and pathway enrichments using the Database for Annotation, Visualization, and Integrated Discovery (DAVID V.6.7) (29 (link), 30 (link)).