The Yes-associated protein YAP, one of the major effectors of the Hippo pathway together with its related protein TAZ, mediates a range of cellular processes from proliferation and death to morphogenesis. YAP and TAZ regulate a large number of target genes, acting as co-activators of DNA-binding transcription factors or as negative regulators of transcription by interacting with the nucleosome remodeling and histone deacetylase complexes. YAP is expressed in self-renewing embryonic stem cells (ESCs), although it is still debated whether it plays any crucial roles in the control of either stemness or differentiation. Here we show that the transient downregulation of YAP in mouse ESCs perturbs cellular homeostasis, leading to the inability to differentiate properly. Bisulfite genomic sequencing revealed that this transient knockdown caused a genome-wide alteration of the DNA methylation remodeling that takes place during the early steps of differentiation, suggesting that the phenotype we observed might be due to the dysregulation of some of the mechanisms involved in regulation of ESC exit from pluripotency. By gene expression analysis we identified two molecules which could have a role in the altered genome-wide methylation profile: the long non-coding RNA Ephemeron, whose rapid upregulation is crucial for ESCs transition into epiblast, and the methyltransferase-like protein Dnmt3l, which, during the embryo development, cooperates with Dnmt3a and Dnmt3b to contribute to the de novo DNA methylation that governs early steps of ESC differentiation. These data suggest a new role for YAP in the governance of the epigenetic dynamics of exit from pluripotency.

YAP contributes to DNA methylation remodeling upon mouse embryonic stem cell differentiation / F. Passaro, I. De Martino, F. Zambelli, G. Di Benedetto, M. Barbato, A.M. D'Erchia, C. Manzari, G. Pesole, M. Mutarelli, D. Cacchiarelli, D. Antonini, S. Parisi, T. Russo. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - (2020). [Epub ahead of print]

YAP contributes to DNA methylation remodeling upon mouse embryonic stem cell differentiation

F. Zambelli
Formal Analysis
;
2020

Abstract

The Yes-associated protein YAP, one of the major effectors of the Hippo pathway together with its related protein TAZ, mediates a range of cellular processes from proliferation and death to morphogenesis. YAP and TAZ regulate a large number of target genes, acting as co-activators of DNA-binding transcription factors or as negative regulators of transcription by interacting with the nucleosome remodeling and histone deacetylase complexes. YAP is expressed in self-renewing embryonic stem cells (ESCs), although it is still debated whether it plays any crucial roles in the control of either stemness or differentiation. Here we show that the transient downregulation of YAP in mouse ESCs perturbs cellular homeostasis, leading to the inability to differentiate properly. Bisulfite genomic sequencing revealed that this transient knockdown caused a genome-wide alteration of the DNA methylation remodeling that takes place during the early steps of differentiation, suggesting that the phenotype we observed might be due to the dysregulation of some of the mechanisms involved in regulation of ESC exit from pluripotency. By gene expression analysis we identified two molecules which could have a role in the altered genome-wide methylation profile: the long non-coding RNA Ephemeron, whose rapid upregulation is crucial for ESCs transition into epiblast, and the methyltransferase-like protein Dnmt3l, which, during the embryo development, cooperates with Dnmt3a and Dnmt3b to contribute to the de novo DNA methylation that governs early steps of ESC differentiation. These data suggest a new role for YAP in the governance of the epigenetic dynamics of exit from pluripotency.
No
English
DNA methylation; Dnmt3l; Ephemeron; cell differentiation; embryonic stem cell; pluripotency; yes-associated protein (YAP)
Settore BIO/11 - Biologia Molecolare
Articolo
Esperti anonimi
Ricerca di base
Pubblicazione scientifica
2020
2-dic-2020
American Society for Biochemistry and Molecular Biology
jbc.RA120.015896
21
Epub ahead of print
Periodico con rilevanza internazionale
pubmed
Aderisco
info:eu-repo/semantics/article
YAP contributes to DNA methylation remodeling upon mouse embryonic stem cell differentiation / F. Passaro, I. De Martino, F. Zambelli, G. Di Benedetto, M. Barbato, A.M. D'Erchia, C. Manzari, G. Pesole, M. Mutarelli, D. Cacchiarelli, D. Antonini, S. Parisi, T. Russo. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - (2020). [Epub ahead of print]
open
Prodotti della ricerca::01 - Articolo su periodico
13
262
Article (author)
si
F. Passaro, I. De Martino, F. Zambelli, G. Di Benedetto, M. Barbato, A.M. D'Erchia, C. Manzari, G. Pesole, M. Mutarelli, D. Cacchiarelli, D. Antonini,...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/797710
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