PLX240790

GSE76023: LncPRESS1 is a p53-regulated lncRNA that safeguards pluripotency by disrupting SIRT6 mediated de-acetylation of histone H3K56

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

Recent evidence suggests that lncRNAs play an integral regulatory role in numerous functions, including determination of cellular identity. We determined global expression (RNA-seq) and genome wide profiles (ChIP-seq) of histone post-translational modifications and p53 binding in human embryonic stem cells (hESCs) undergoing differentiation to define a high-confidence set of 40 lncRNAs, which are p53 transcriptional targets. We focused on lncRNAs, highly expressed in pluripotent hESCs and repressed by p53 during differentiation, to identify lncPRESS1 as a p53-regulated transcript that maintains hESC pluripotency in concert with core pluripotency factors. RNA-seq of hESCs depleted of lncPRESS1 revealed that lncPRESS1 controls a gene network that promotes pluripotency. Further, we found that lncPRESS1 physically interacts with SIRT6 to prevent SIRT6 chromatin localization and maintain high levels of histone H3K56 and H3K9 acetylation at promoters of pluripotency genes. In summary, we describe a novel pluripotency-specific lncRNA that safeguards the hESC state by disrupting SIRT6 activity SOURCE: Yuanxin Xi (xiyuanxin@yahoo.com) - The University of Texas MD Anderson Cancer Center