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B1 SINE-binding ZFP...
B1 SINE-binding ZFP266 impedes mouse iPSC generation through suppression of chromatin opening mediated by reprogramming factors
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- Kaemena, DF (author)
- University of Edinburgh
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- Yoshihara, M (author)
- Karolinska Institute,Karolinska Institutet
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- Beniazza, M (author)
- University of Edinburgh
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- Ashmore, J (author)
- University of Edinburgh
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- Zhao, SL (author)
- University of Edinburgh
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- Bertenstam, Mårten (author)
- Lund University,Lunds universitet,Beräkningsbiologi och biologisk fysik - Har omorganiserats,Institutionen för astronomi och teoretisk fysik - Har omorganiserats,Naturvetenskapliga fakulteten,Computational Biology and Biological Physics - Has been reorganised,Department of Astronomy and Theoretical Physics - Has been reorganised,Faculty of Science
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- Olariu, Victor (author)
- Lund University,Lunds universitet,Beräkningsbiologi och biologisk fysik - Har omorganiserats,Institutionen för astronomi och teoretisk fysik - Har omorganiserats,Naturvetenskapliga fakulteten,Computational Biology and Biological Physics - Has been reorganised,Department of Astronomy and Theoretical Physics - Has been reorganised,Faculty of Science
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- Katayama, S (author)
- Karolinska Institute,Karolinska Institutet,University of Helsinki,Folkhälsan Research Center
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Okita, K (author)
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- Tomlinson, SR (author)
- University of Edinburgh
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Yusa, K (author)
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- Kaji, K (author)
- University of Edinburgh
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(creator_code:org_t)
- 2023-01-30
- 2023
- English.
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1, s. 488-
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Abstract
Subject headings
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- Induced pluripotent stem cell (iPSC) reprogramming is inefficient and understanding the molecular mechanisms underlying this inefficiency holds the key to successfully control cellular identity. Here, we report 24 reprogramming roadblock genes identified by CRISPR/Cas9-mediated genome-wide knockout (KO) screening. Of these, depletion of the predicted KRAB zinc finger protein (KRAB-ZFP) Zfp266 strongly and consistently enhances murine iPSC generation in several reprogramming settings, emerging as the most robust roadblock. We show that ZFP266 binds Short Interspersed Nuclear Elements (SINEs) adjacent to binding sites of pioneering factors, OCT4 (POU5F1), SOX2, and KLF4, and impedes chromatin opening. Replacing the KRAB co-suppressor with co-activator domains converts ZFP266 from an inhibitor to a potent facilitator of iPSC reprogramming. We propose that the SINE-KRAB-ZFP interaction is a critical regulator of chromatin accessibility at regulatory elements required for efficient cellular identity changes. In addition, this work serves as a resource to further illuminate molecular mechanisms hindering reprogramming.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Kaemena, DF
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Yoshihara, M
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Beniazza, M
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Ashmore, J
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Zhao, SL
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Bertenstam, Mårt ...
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show more...
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Olariu, Victor
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Katayama, S
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Okita, K
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Tomlinson, SR
-
Yusa, K
-
Kaji, K
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Nature communica ...
- By the university
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Karolinska Institutet
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Lund University