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Article

Cruciform Formable Sequences within Pou5f1 Enhancer Are Indispensable for Mouse ES Cell Integrity

by 1,2, 2 and 1,2,*
1
Department of Biology, Faculty of Education and Integrated Arts and Sciences, Waseda University, Shinjuku-ku, Tokyo 162-8480, Japan
2
Major in Integrative Bioscience and Biomedical Engineering, Graduate School of Science and Engineering, Waseda University, Shinjuku-ku, Tokyo 162-8480, Japan
*
Author to whom correspondence should be addressed.
Academic Editors: Masato Katahira and Joon-Hwa Lee
Int. J. Mol. Sci. 2021, 22(7), 3399; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22073399
Received: 17 February 2021 / Revised: 22 March 2021 / Accepted: 22 March 2021 / Published: 26 March 2021
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. View Full-Text
Keywords: inverted repeat (IR) sequence; cruciform; super-enhancer; eRNA; mouse ES cells; Pou5f1 (Oct3/4); Sox2; Nanog; Klf4; Esrrb inverted repeat (IR) sequence; cruciform; super-enhancer; eRNA; mouse ES cells; Pou5f1 (Oct3/4); Sox2; Nanog; Klf4; Esrrb
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MDPI and ACS Style

Yamamoto, Y.; Miura, O.; Ohyama, T. Cruciform Formable Sequences within Pou5f1 Enhancer Are Indispensable for Mouse ES Cell Integrity. Int. J. Mol. Sci. 2021, 22, 3399. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22073399

AMA Style

Yamamoto Y, Miura O, Ohyama T. Cruciform Formable Sequences within Pou5f1 Enhancer Are Indispensable for Mouse ES Cell Integrity. International Journal of Molecular Sciences. 2021; 22(7):3399. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22073399

Chicago/Turabian Style

Yamamoto, Yu, Osamu Miura, and Takashi Ohyama. 2021. "Cruciform Formable Sequences within Pou5f1 Enhancer Are Indispensable for Mouse ES Cell Integrity" International Journal of Molecular Sciences 22, no. 7: 3399. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22073399

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