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. ATAC seq profiling to explore diferences in the genome-wide chromatin accessibitlity in fibrotic and. naïve corneas

伤口愈合级联反应失调常可导致角膜纤维化。越来越多的证据表明，表观遗传学（epigenetics）是驱动角膜纤维化的调控机制之一。本研究以碱诱导角膜纤维化的家兔模型为研究对象，采用ATAC-Seq技术鉴定驱动该疾病病理进程的转录因子与基因调控元件，以此探究该模型中碱诱导角膜纤维化所引发的表观遗传调控变化。我们在纤维化角膜中观察到广泛的表观基因组重编程，其特征为染色质可及性降低、启动子向增强子的调控转换，以及纤维化相关转录网络的选择性激活。本研究鉴定出多个经典已知转录因子基序（包括Sp1、KLF9、NFY、KLF4与ETV4），以及与KLF17、NRF、ETV6具有相似性的全新基序，这些基序可作为潜在的表观遗传学靶点，用于后续角膜纤维化治疗策略的评估与开发。本研究通过ATAC-Seq分析，旨在探究纤维化角膜与正常角膜之间全基因组范围内的染色质可及性差异。