PRJNA433566
Heterochromatin H3K9me3 ChIP-seq on retinal pigment epithelial cell ARPE-19 cells
Oxidative stress (OS)-induced retinal pigment epithelium (RPE) cell apoptosis is critically implicated in the pathogenesis of age-related macular degeneration (AMD), a leading cause for blindness in the elderly. Heterochromatin, a compact and transcriptional inert chromatin structure, has been recently shown to be dynamically regulated in response to stress stimuli. The functional mechanism of heterochromatin upon OS exposure is unclear. Here, we show that OS increases heterochromatin formation both in vivo and in vitro, which is essential for protecting RPE cells from oxidative damage. Chromatin immunoprecipitation (ChIP)-seq demonstrates that OS-induced heterochromatin selectively accumulates at p53-regulated proapoptotic target promoters and inhibits gene expression. Furthermore, OS-induced desumoylation of p53 promotes p53-heterchromatin interaction and regulates p53 promoter selection, resulting in the locus-specific recruitment of heterochromatin and transcription repression. Together, our findings demonstrate a new protective function of OS-induced heterochromatin formation. We further show that p53 desumoylation and consequent heterochromatin recruitment play a critical role in p53-regualted OS response function. We propose that targeting heterochromatin provides a plausible therapeutic strategy for the treatment of AMD.