Tissue-specific chromatin accessibility cis-regulatory regions in rat white adipose and muscle

Chromatin accessibility is a key factor influencing gene expression. We developed a modified protocol, ruptor-ATAC, which with RNA-seq was used to investigate regulatory elements underlying gene expression in rat white adipose and skeletal muscle, two tissues with contrasting metabolic functions. Integration of both datasets showed that promoter accessibility correlated with RNA expression and identified 44,798 tissue-specific differentially accessible regions (DARs), predominantly localized in intergenic and intron regions. Tissue-specific DARs mapped to differentially expressed genes that were enriched in distinct biological processes. Motif enrichment analysis on DARs predicted binding sites for transcription factors (TFs). Significant up-regulation of 11 TFs recognizing enriched cis-motifs in each tissue indicated their functional relevance. Positive correlation between motif accessibility and target gene expression further supported the role of selected TFs as transcriptional regulators. Our study identifies non-promoter cis-regulatory regions that likely play a major role in the control of tissue-specific gene expression in adipose and muscle. RNA sequencing was performed on 10 gastrocnemius muscle (skeletal muscle) samples and 10 abdominal white adipose tissue (WAT) samples dissected from Fischer 344 x Brown Norway (F344BN) rats. Tissue samples were obtained from 10 individual animals, namely 5 males and 5 females.