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

TitleFine-Tuning Mybl2 Is Required for Proper Mesenchymal-to-Epithelial Transition during Somatic Reprogramming.
Publication TypeJournal Article
Year of Publication2018
AuthorsWard C, Volpe G, Cauchy P, Ptasinska A, Almaghrabi R, Blakemore D, Nafria M, Kestner D, Frampton J, Murphy G, Buganim Y, Kaji K, García P
JournalCell Rep
Volume24
Issue6
Pagination1496-1511.e8
Date Published2018 Aug 07
ISSN2211-1247
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.

DOI10.1016/j.celrep.2018.07.026
Alternate JournalCell Rep
PubMed ID30089261
PubMed Central IDPMC6092268
Grant List / / Wellcome Trust / United Kingdom
Publication institute
CRM