LncPRESS1 Is a p53-Regulated LncRNA that Safeguards Pluripotency by Disrupting SIRT6-Mediated De-acetylation of Histone H3K56

Abhinav K. Jain, Yuanxin Xi, Ryan McCarthy, Kendra Allton, Kadir C. Akdemir, Lalit R. Patel, Bruce Aronow, Chunru Lin, Wei Li, Liuqing Yang, Michelle C. Barton

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)967-981
Number of pages15
JournalMolecular Cell
Volume64
Issue number5
DOIs
StatePublished - Dec 1 2016
Externally publishedYes

Keywords

  • chromatin
  • differentiation
  • genome-wide
  • H3K56ac
  • H3K9ac
  • hESC
  • lncRNA
  • p53
  • pluripotency
  • SIRT6

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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