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Cell Rep. 2018 Aug 7;24(6):1496-1511.e8. doi: 10.1016/j.celrep.2018.07.026.

Fine-Tuning Mybl2 Is Required for Proper Mesenchymal-to-Epithelial Transition during Somatic Reprogramming.

Author information

1
Institute of Cancer and Genomic Science, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
2
Institute of Cancer and Genomic Science, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK; Department of Molecular and Cellular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
3
Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
4
The Institute for Medical Research Israel-Canada, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
5
MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK.
6
Institute of Cancer and Genomic Science, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK. Electronic address: p.garcia@bham.ac.uk.

Abstract

During somatic reprogramming, Yamanaka's pioneer factors regulate a complex sequence of molecular events leading to the activation of a network of pluripotency factors, ultimately resulting in the acquisition and maintenance of a pluripotent state. Here, we show that, contrary to the pluripotency factors studied so far, overexpression of Mybl2 inhibits somatic reprogramming. Our results demonstrate that Mybl2 levels are crucial to the dynamics of the reprogramming process. Mybl2 overexpression changes chromatin conformation, affecting the accessibility of pioneer factors to the chromatin and promoting accessibility for early immediate response genes known to be reprogramming blockers. These changes in the chromatin landscape ultimately lead to a deregulation of key genes that are important for the mesenchymal-to-epithelial transition. This work defines Mybl2 level as a gatekeeper for the initiation of reprogramming, providing further insights into the tight regulation and required coordination of molecular events that are necessary for changes in cell fate identity during the reprogramming process.

KEYWORDS:

AP1; ATAC-sequencing; Jun; Sox2; chromatin landscape; chromatin remodeling; induced pluripotent stem cells; mesenchymal-to-epithelial transition; reprogramming blockers; somatic reprogramming

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