HSF4/COIL complex-dependent R-loop mediates ultraviolet-induced inflammatory skin injury.
Yi-Qian FengHeng ZhangJing-Xia HanBi-Jia CuiLu-Ning QinLei ZhangQing-Qing LiXin-Ying WuNan-Nan XiaoYan ZhangTing-Ting LinHui-Juan LiuTao SunPublished in: Clinical and translational medicine (2023)
Intense ultraviolet (UV) exposure can cause phototoxic reactions, such as skin inflammation, resulting in injury. UV is a direct cause of DNA damage, but the mechanisms underlying transcriptional regulation within cells after DNA damage are unclear. The bioinformatics analysis of transcriptome sequencing data from UV-irradiated and non-UV-irradiated skin showed that transcription-related proteins, such as HSF4 and COIL, mediate cellular response to UV irradiation. HSF4 and COIL can form a complex under UV irradiation, and the preference for binding target genes changed because of the presence of a large number of R-loops in cells under UV irradiation and the ability of COIL to recognize R-loops. The regulation of target genes was altered by the HSF4-COIL complex, and the expression of inflammation and ageing-related genes, such as Atg7, Tfpi, and Lims1, was enhanced. A drug screen was performed for the recognition sites of COIL and R-loop. N6-(2-hydroxyethyl)-adenosine can competitively bind COIL and inhibit the binding of COIL to the R-loop. Thus, the activation of downstream inflammation-related genes and inflammatory skin injury was inhibited.
Keyphrases
- oxidative stress
- dna damage
- induced apoptosis
- heat shock
- diabetic rats
- soft tissue
- transcription factor
- wound healing
- genome wide
- cell cycle arrest
- aqueous solution
- single cell
- gene expression
- dna repair
- binding protein
- high throughput
- cell death
- rna seq
- machine learning
- long non coding rna
- artificial intelligence
- heat stress
- heat shock protein