Comprehensive Analysis of Chromatin Accessibility and Transcriptional Landscape Identified BRCA1 Repression as a Potential Pathological Factor for Keloid

Keloid is a poorly understood fibrotic skin disease that commonly occurs during wound-healing. As a polymer composed of nucleic acid and proteins, the structure of chromatin could be dynamically regulated in the nucleus. In this study, we explored the dynamics of chromatin accessibility and the transcriptome in dermal fibroblasts (DFs) in keloid formation. Compared to normal samples, chromatin accessibility and transcriptome were extensively altered in keloid DFs. In addition, changes in chromatin accessibility were closely associated with changes in gene expression in DFs. Breast cancer type 1 (BRCA1) was significantly downregulated in keloid DFs, and its knockdown promoted the proliferation and attenuated the migration ability of normal DF cells. Mechanistically, BRCA1 suppression significantly reduced the expression of neuronal pentraxin 2 (NPTX2), a cell viability-related gene. BRCA1 binding affinity at the NPTX2 enhancer and the chromatin accessibility in the same region were significantly lower in keloid DFs than in normal DFs, which might contribute to NPTX2 inhibition. In conclusion, this study identified BRCA1 inhibition in DFs as a novel pathological factor in keloids and preliminarily explored its potential mechanisms, which will help us understand the formation of keloids.

Automated summary

This study investigated the dynamic changes of chromatin accessibility and the transcriptome in dermal fibroblasts (DFs) during keloid formation. The results showed extensive alterations in chromatin accessibility and transcriptome in keloid DFs compared to normal samples. In addition, the downregulation of BRCA1 in keloid DFs was found to be closely associated with changes in gene expression, which may contribute to the formation of keloids.