LncPRESS1 Is a p53 Regulated LncRNA that Safeguards Pluripotency by Disrupting SIRT6 Mediated De acetylation of Histone H3K56.
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 and prevents SIRT6 chromatin localization, which maintains high levels of histone H3K56 and H3K9 acetylation at promoters of pluripotency genes. In summary, we describe a p53 regulated, pluripotency specific lncRNA that safeguards the hESC state by disrupting SIRT6 activity.
Molecular cell