Cargando…
The ETS transcription factor ERF controls the exit from the naïve pluripotent state in a MAPK-dependent manner
The naïve epiblast transitions to a pluripotent primed state during embryo implantation. Despite the relevance of the FGF pathway during this period, little is known about the downstream effectors regulating this signaling. Here, we examined the molecular mechanisms coordinating the naïve to primed...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10292047/ https://www.ncbi.nlm.nih.gov/pubmed/34597136 http://dx.doi.org/10.1126/sciadv.abg8306 |
_version_ | 1785062805587623936 |
---|---|
author | Vega-Sendino, Maria Olbrich, Teresa Tillo, Desiree Tran, Andy D. Domingo, Catherine N. Franco, Mariajose FitzGerald, Peter C. Kruhlak, Michael J. Ruiz, Sergio |
author_facet | Vega-Sendino, Maria Olbrich, Teresa Tillo, Desiree Tran, Andy D. Domingo, Catherine N. Franco, Mariajose FitzGerald, Peter C. Kruhlak, Michael J. Ruiz, Sergio |
author_sort | Vega-Sendino, Maria |
collection | PubMed |
description | The naïve epiblast transitions to a pluripotent primed state during embryo implantation. Despite the relevance of the FGF pathway during this period, little is known about the downstream effectors regulating this signaling. Here, we examined the molecular mechanisms coordinating the naïve to primed transition by using inducible ESC to genetically eliminate all RAS proteins. We show that differentiated RAS(KO) ESC remain trapped in an intermediate state of pluripotency with naïve-associated features. Elimination of the transcription factor ERF overcomes the developmental blockage of RAS-deficient cells by naïve enhancer decommissioning. Mechanistically, ERF regulates NANOG expression and ensures naïve pluripotency by strengthening naïve transcription factor binding at ESC enhancers. Moreover, ERF negatively regulates the expression of the methyltransferase DNMT3B, which participates in the extinction of the naïve transcriptional program. Collectively, we demonstrated an essential role for ERF controlling the exit from naïve pluripotency in a MAPK-dependent manner during the progression to primed pluripotency. |
format | Online Article Text |
id | pubmed-10292047 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-102920472023-06-26 The ETS transcription factor ERF controls the exit from the naïve pluripotent state in a MAPK-dependent manner Vega-Sendino, Maria Olbrich, Teresa Tillo, Desiree Tran, Andy D. Domingo, Catherine N. Franco, Mariajose FitzGerald, Peter C. Kruhlak, Michael J. Ruiz, Sergio Sci Adv Biomedicine and Life Sciences The naïve epiblast transitions to a pluripotent primed state during embryo implantation. Despite the relevance of the FGF pathway during this period, little is known about the downstream effectors regulating this signaling. Here, we examined the molecular mechanisms coordinating the naïve to primed transition by using inducible ESC to genetically eliminate all RAS proteins. We show that differentiated RAS(KO) ESC remain trapped in an intermediate state of pluripotency with naïve-associated features. Elimination of the transcription factor ERF overcomes the developmental blockage of RAS-deficient cells by naïve enhancer decommissioning. Mechanistically, ERF regulates NANOG expression and ensures naïve pluripotency by strengthening naïve transcription factor binding at ESC enhancers. Moreover, ERF negatively regulates the expression of the methyltransferase DNMT3B, which participates in the extinction of the naïve transcriptional program. Collectively, we demonstrated an essential role for ERF controlling the exit from naïve pluripotency in a MAPK-dependent manner during the progression to primed pluripotency. American Association for the Advancement of Science 2021-10-01 /pmc/articles/PMC10292047/ /pubmed/34597136 http://dx.doi.org/10.1126/sciadv.abg8306 Text en Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Vega-Sendino, Maria Olbrich, Teresa Tillo, Desiree Tran, Andy D. Domingo, Catherine N. Franco, Mariajose FitzGerald, Peter C. Kruhlak, Michael J. Ruiz, Sergio The ETS transcription factor ERF controls the exit from the naïve pluripotent state in a MAPK-dependent manner |
title | The ETS transcription factor ERF controls the exit from the naïve pluripotent state in a MAPK-dependent manner |
title_full | The ETS transcription factor ERF controls the exit from the naïve pluripotent state in a MAPK-dependent manner |
title_fullStr | The ETS transcription factor ERF controls the exit from the naïve pluripotent state in a MAPK-dependent manner |
title_full_unstemmed | The ETS transcription factor ERF controls the exit from the naïve pluripotent state in a MAPK-dependent manner |
title_short | The ETS transcription factor ERF controls the exit from the naïve pluripotent state in a MAPK-dependent manner |
title_sort | ets transcription factor erf controls the exit from the naïve pluripotent state in a mapk-dependent manner |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10292047/ https://www.ncbi.nlm.nih.gov/pubmed/34597136 http://dx.doi.org/10.1126/sciadv.abg8306 |
work_keys_str_mv | AT vegasendinomaria theetstranscriptionfactorerfcontrolstheexitfromthenaivepluripotentstateinamapkdependentmanner AT olbrichteresa theetstranscriptionfactorerfcontrolstheexitfromthenaivepluripotentstateinamapkdependentmanner AT tillodesiree theetstranscriptionfactorerfcontrolstheexitfromthenaivepluripotentstateinamapkdependentmanner AT tranandyd theetstranscriptionfactorerfcontrolstheexitfromthenaivepluripotentstateinamapkdependentmanner AT domingocatherinen theetstranscriptionfactorerfcontrolstheexitfromthenaivepluripotentstateinamapkdependentmanner AT francomariajose theetstranscriptionfactorerfcontrolstheexitfromthenaivepluripotentstateinamapkdependentmanner AT fitzgeraldpeterc theetstranscriptionfactorerfcontrolstheexitfromthenaivepluripotentstateinamapkdependentmanner AT kruhlakmichaelj theetstranscriptionfactorerfcontrolstheexitfromthenaivepluripotentstateinamapkdependentmanner AT ruizsergio theetstranscriptionfactorerfcontrolstheexitfromthenaivepluripotentstateinamapkdependentmanner AT vegasendinomaria etstranscriptionfactorerfcontrolstheexitfromthenaivepluripotentstateinamapkdependentmanner AT olbrichteresa etstranscriptionfactorerfcontrolstheexitfromthenaivepluripotentstateinamapkdependentmanner AT tillodesiree etstranscriptionfactorerfcontrolstheexitfromthenaivepluripotentstateinamapkdependentmanner AT tranandyd etstranscriptionfactorerfcontrolstheexitfromthenaivepluripotentstateinamapkdependentmanner AT domingocatherinen etstranscriptionfactorerfcontrolstheexitfromthenaivepluripotentstateinamapkdependentmanner AT francomariajose etstranscriptionfactorerfcontrolstheexitfromthenaivepluripotentstateinamapkdependentmanner AT fitzgeraldpeterc etstranscriptionfactorerfcontrolstheexitfromthenaivepluripotentstateinamapkdependentmanner AT kruhlakmichaelj etstranscriptionfactorerfcontrolstheexitfromthenaivepluripotentstateinamapkdependentmanner AT ruizsergio etstranscriptionfactorerfcontrolstheexitfromthenaivepluripotentstateinamapkdependentmanner |