BCL11A deficiency protects epidermis from UVB-induced damage through promotion of autophagy.

Abstract

As a major environmental pathogenic factor for various skin diseases, UVB radiation leads to oxidative stress and biomacromolecule damage. Autophagy is a highly conserved catabolic process and serves as one of the main mechanisms to maintain cellular homeostasis. Here, by CRISPR/Cas9-mediated gene deletion, we demonstrate that the essential transcriptional repressor BCL11A is involved in autophagy regulation and participates in the UVB-induced stress response. BCL11A deficiency increases autophagosome formation and enhances the intensity of autophagy flux with or without UVB stress. Mechanistically, ACSS3, rather than autophagy-related genes, is identified as the direct target gene and transcriptionally repressed by BCL11A. Further, BCL11A deficiency reduces DNA damage and ROS to promote survival and inhibit apoptosis under UVB irradiation, which is blocked by pharmacological inhibition of autophagy or BCL11A overexpression. Collectively, BCL11A deficiency promotes autophagy activation to clear ROS and DNA damage, thereby protecting epidermal cells from UVB-induced death.