PURPL plays a role in epigenetic regulation of gene expression [ChIP-Seq]

Cellular senescence involves heterochromatin reorganization and aberrant gene expression. We demonstrate that the nuclear-enriched lncRNA PURPL regulates senescence-associated chromatin dynamics by modulating H3K9me3 deposition. PURPL knockdown increased global H3K9me3 levels while its overexpression reduced this repressive mark. Genome-wide analysis revealed 411 loci with PURPL-dependent H3K9me3 changes, including the aging-related gene SERPINE1, where H3K9me3 accumulation correlated with transcriptional repression. These findings establish PURPL as an epigenetic regulator of senescence through targeted control of heterochromatin formation. Overall design: ChIP-seq of CRISPRi-mediated PURPL knockdown and control cell lines.

细胞衰老（cellular senescence）涉及异染色质重排与异常基因表达。本研究证实，核富集型长链非编码RNA（long non-coding RNA, lncRNA）PURPL通过调控组蛋白H3赖氨酸9三甲基化（H3K9me3）的沉积，调控衰老相关染色质动态变化过程。敲低PURPL会提升全局H3K9me3水平，而过表达PURPL则会降低该抑制性组蛋白修饰标记的丰度。全基因组分析共鉴定出411个受PURPL调控的H3K9me3修饰变化基因座，其中包括衰老相关基因SERPINE1；该基因座的H3K9me3富集水平与其转录抑制程度呈显著正相关。上述研究结果证实，PURPL通过靶向调控异染色质形成，成为细胞衰老的表观遗传调控因子。实验设计：对CRISPR干扰（CRISPR interference, CRISPRi）介导的PURPL敲低细胞系及对照细胞系开展染色质免疫共沉淀测序（chromatin immunoprecipitation sequencing, ChIP-seq）。