Differential analysis of chromatin accessibility and gene expression profiles identifies cis-regulatory elements in rat adipose and muscle

Chromatin accessibility is a key factor influencing gene expression. We developed a modified protocol, ruptor-ATAC, which together with RNA-seq was used to investigate regulatory elements underlying tissue-specific gene expression in rat white adipose and skeletal muscle, two tissues with contrasting metabolic functions. While promoter accessibility correlated with RNA expression, integration of the two datasets identified tissue-specific differentially accessible regions (DARs) that predominantly localized in intergenic and intron regions. DARs mapped to differentially expressed genes that were enriched in distinct biological processes in each tissue. Motif enrichment analysis on tissue-specific DARs predicted binding sites for transcription factors (TFs), several of which were up-regulated in the corresponding tissue. Positive relationship between DARs and target gene expression further supported a functional role for these TF binding motifs. Our study identifies cis-regulatory regions that likely play a major role in the regulation of tissue-specific gene expression in adipose and muscle. ATAC-seq was performed on 9 abdominal white adipose tissue (WAT) and 9 gastrocnemius muscle (skeletal muscle) tissue samples obtained from Fischer 344 rats. Tissue samples were either collected from individual animals, or represented pulverized aliquots of tissues pooled from 15 males.