ATAC-seq revealing chromatin accessibility and novel motifs linked to corneal fibrosis

Dysregulation of wound healing cascade often results in corneal fibrosis. Increasingly evidence suggest the role of epigentics as one of the regulatory mechanisms that drive corneal fibrosis. The present study investigated epigenetic modulation caused by alkali-induced corneal fibrosis in rabbit model by employing ATAC-Seq to identify transcription factors and gene regulatory elements that drive the disease pathology. We observed a extensive epigenomic reprogramming characterized by reduced chromatin accessibility, promoter-to-enhancer regulatory shifts and selective activation of fibrosis-associated transcriptional networks in the fibrotic corneas. Key known (Sp1, KLF9, NFY, KLF4, and ETV4) and de novo motifs shwoing similarity to KLF17, NRF, and ETV6 were identified that could serve as potential epigenetic tragets for further evaluation as therapeutic approach in treating corneal fibrosis. Overall design: ATAC seq profiling to explore diferences in the genome-wide chromatin accessibitlity in fibrotic and. naïve corneas