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OCT4 impedes cell fate redirection by the melanocyte lineage master regulator MITF

Danna Sheinboim, Itay Maza, Iris Dror, Shivang Parikh, Vladislav Krupalnik, Rachel E Bell, Asaf Zviran, Yusuke Suita, Ofir Hakim, Yael Mandel Gutfreund, Mehdi Khaled, View ORCID ProfileJacob H Hanna, Carmit Levy
doi: https://doi.org/10.1101/142943
Danna Sheinboim
1Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
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Itay Maza
2Department of Molecular Genetics, Weizmann Institute, Rehovot, Israel
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Iris Dror
3Department of Biology, Technion – Israel Institute of Technology, Haifa 32000, Israel
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Shivang Parikh
1Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
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Vladislav Krupalnik
2Department of Molecular Genetics, Weizmann Institute, Rehovot, Israel
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Rachel E Bell
1Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
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Asaf Zviran
2Department of Molecular Genetics, Weizmann Institute, Rehovot, Israel
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Yusuke Suita
4Cutaneous Biology Research Center, Department of Dermatology and MGH Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA
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Ofir Hakim
5The Mina and Everard Goodman Faculty of Life Sciences Bar-Ilan University, Ramat Gan 5290002, Israel
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Yael Mandel Gutfreund
3Department of Biology, Technion – Israel Institute of Technology, Haifa 32000, Israel
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Mehdi Khaled
6Institut Gustave Roussy, INSERM 1186, Villejuif 94805, France
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Jacob H Hanna
2Department of Molecular Genetics, Weizmann Institute, Rehovot, Israel
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  • ORCID record for Jacob H Hanna
  • For correspondence: carmitlevy@post.tau.ac.il jacob.hanna@weizmann.ac.il
Carmit Levy
1Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
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  • For correspondence: carmitlevy@post.tau.ac.il jacob.hanna@weizmann.ac.il
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ABSTRACT

Ectopic expression of lineage master regulators induces transdifferentiation. Whether cell fate transitions can be induced during various developmental stages has never been systemically examined. Here we discovered that amongst different developmental stages, embryonic stem cells (ESCs) were resistant to cell fate conversion induced by the melanocyte lineage master regulator MITF. We generated a transgenic system and found that in ESCs, the pluripotency master regulator, OCT4, counteracts pro-differentiation induced by MITF by physical interference with MITF transcriptional activity. We further found that ESCs must be released from OCT4-maintained pluripotency prior to ectopically induced differentiation. Moreover, OCT4 induction in various differentiated cells repressed their lineage identity in vivo. Alongside, chromatin architecture combined with ChIP-seq analysis suggested that OCT4 competes with various lineage master regulators for binding promoters and enhancers. Our analysis reveals pluripotency and transdifferentiation regulatory principles and could open new opportunities in the field of regenerative medicine.

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Posted May 27, 2017.
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OCT4 impedes cell fate redirection by the melanocyte lineage master regulator MITF
Danna Sheinboim, Itay Maza, Iris Dror, Shivang Parikh, Vladislav Krupalnik, Rachel E Bell, Asaf Zviran, Yusuke Suita, Ofir Hakim, Yael Mandel Gutfreund, Mehdi Khaled, Jacob H Hanna, Carmit Levy
bioRxiv 142943; doi: https://doi.org/10.1101/142943
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OCT4 impedes cell fate redirection by the melanocyte lineage master regulator MITF
Danna Sheinboim, Itay Maza, Iris Dror, Shivang Parikh, Vladislav Krupalnik, Rachel E Bell, Asaf Zviran, Yusuke Suita, Ofir Hakim, Yael Mandel Gutfreund, Mehdi Khaled, Jacob H Hanna, Carmit Levy
bioRxiv 142943; doi: https://doi.org/10.1101/142943

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