Cruciform formable sequences within pou5f1 enhancer are indispensable for mouse es cell integrity

Yu Yamamoto, Osamu Miura, Takashi Ohyama

Research output: Contribution to journalArticlepeer-review

Abstract

DNA can adopt various structures besides the B-form. Among them, cruciform structures are formed on inverted repeat (IR) sequences. While cruciform formable IRs (CFIRs) are sometimes found in regulatory regions of transcription, their function in transcription remains elusive, especially in eukaryotes. We found a cluster of CFIRs within the mouse Pou5f1 enhancer. Here, we demonstrate that this cluster or some member(s) plays an active role in the transcriptional regulation of not only Pou5f1, but also Sox2, Nanog, Klf4 and Esrrb. To clarify in vivo function of the cluster, we performed genome editing using mouse ES cells, in which each of the CFIRs was altered to the corresponding mirror repeat sequence. The alterations reduced the level of the Pou5f1 transcript in the genome-edited cell lines, and elevated those of Sox2, Nanog, Klf4 and Esrrb. Furthermore, transcription of non-coding RNAs (ncRNAs) within the enhancer was also upregulated in the genome-edited cell lines, in a similar manner to Sox2, Nanog, Klf4 and Esrrb. These ncRNAs are hypothesized to control the expression of these four pluripotency genes. The CFIRs present in the Pou5f1 enhancer seem to be important to maintain the integrity of ES cells.

Original languageEnglish
Article number3399
JournalInternational journal of molecular sciences
Volume22
Issue number7
DOIs
Publication statusPublished - 2021 Apr 1

Keywords

  • Cruciform
  • ERNA
  • Esrrb
  • Inverted repeat (IR) sequence
  • Klf4
  • Mouse ES cells
  • Nanog
  • Pou5f1 (Oct3/4)
  • Sox2
  • Super-enhancer

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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