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A novel member of Prame family, Gm12794c, counteracts retinoic acid differentiation through the methyltransferase activity of PRC2.

Napolitano, Giuliana and Tagliaferri, Daniela and Fusco, Salvatore and Cirillo, Carmine and De Martino, Ilaria and Addeo, Martina and Mazzone, Pellegrino and Russo, Nicola Antonino and Natale, Francesco and Cardoso, M. Cristina and De Luca, Luciana and Lamorte, Daniela and La Rocca, Francesco and De Felice, Mario and Falco, Geppino (2020):
A novel member of Prame family, Gm12794c, counteracts retinoic acid differentiation through the methyltransferase activity of PRC2.
In: Cell death and differentiation, (1), 27. pp. 345-362, ISSN 1476-5403,
DOI: 10.1038/s41418-019-0359-9,
[Article]

Abstract

Embryonic stem cells (ESCs) fluctuate among different levels of pluripotency defined as metastates. Sporadically, metastable cellular populations convert to a highly pluripotent metastate that resembles the preimplantation two-cell embryos stage (defined as 2C stage) in terms of transcriptome, DNA methylation, and chromatin structure. Recently, we found that the retinoic acid (RA) signaling leads to a robust increase of cells specifically expressing 2C genes, such as members of the Prame family. Here, we show that Gm12794c, one of the most highly upregulated Prame members, and previously identified as a key player for the maintenance of pluripotency, has a functional role in conferring ESCs resistance to RA signaling. In particular, RA-dependent expression of Gm12794c induces a ground state-like metastate, as evaluated by activation of 2C-specific genes, global DNA hypomethylation and rearrangement of chromatin similar to that observed in naive totipotent preimplantation epiblast cells and 2C-like cells. Mechanistically, we demonstrated that Gm12794c inhibits Cdkn1A gene expression through the polycomb repressive complex 2 (PRC2) histone methyltransferase activity. Collectively, our data highlight a molecular mechanism employed by ESCs to counteract retinoic acid differentiation stimuli and contribute to shed light on the molecular mechanisms at grounds of ESCs naive pluripotency-state maintenance.

Item Type: Article
Erschienen: 2020
Creators: Napolitano, Giuliana and Tagliaferri, Daniela and Fusco, Salvatore and Cirillo, Carmine and De Martino, Ilaria and Addeo, Martina and Mazzone, Pellegrino and Russo, Nicola Antonino and Natale, Francesco and Cardoso, M. Cristina and De Luca, Luciana and Lamorte, Daniela and La Rocca, Francesco and De Felice, Mario and Falco, Geppino
Title: A novel member of Prame family, Gm12794c, counteracts retinoic acid differentiation through the methyltransferase activity of PRC2.
Language: English
Abstract:

Embryonic stem cells (ESCs) fluctuate among different levels of pluripotency defined as metastates. Sporadically, metastable cellular populations convert to a highly pluripotent metastate that resembles the preimplantation two-cell embryos stage (defined as 2C stage) in terms of transcriptome, DNA methylation, and chromatin structure. Recently, we found that the retinoic acid (RA) signaling leads to a robust increase of cells specifically expressing 2C genes, such as members of the Prame family. Here, we show that Gm12794c, one of the most highly upregulated Prame members, and previously identified as a key player for the maintenance of pluripotency, has a functional role in conferring ESCs resistance to RA signaling. In particular, RA-dependent expression of Gm12794c induces a ground state-like metastate, as evaluated by activation of 2C-specific genes, global DNA hypomethylation and rearrangement of chromatin similar to that observed in naive totipotent preimplantation epiblast cells and 2C-like cells. Mechanistically, we demonstrated that Gm12794c inhibits Cdkn1A gene expression through the polycomb repressive complex 2 (PRC2) histone methyltransferase activity. Collectively, our data highlight a molecular mechanism employed by ESCs to counteract retinoic acid differentiation stimuli and contribute to shed light on the molecular mechanisms at grounds of ESCs naive pluripotency-state maintenance.

Journal or Publication Title: Cell death and differentiation
Number: 1
Divisions: 10 Department of Biology
10 Department of Biology > Cell Biology and Epigenetics
Date Deposited: 18 Jun 2019 08:22
DOI: 10.1038/s41418-019-0359-9
Identification Number: pmid:31186534
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