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Dynamic antagonism between key repressive pathways maintains the placental epigenome
DNA and Histone 3 Lysine 27 methylation typically function as repressive modifications and operate within distinct genomic compartments. In mammals, the majority of the genome is kept in a DNA methylated state, whereas the Polycomb repressive complexes regulate the unmethylated CpG-rich promoters of...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10104784/ https://www.ncbi.nlm.nih.gov/pubmed/37024684 http://dx.doi.org/10.1038/s41556-023-01114-y |
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author | Weigert, Raha Hetzel, Sara Bailly, Nina Haggerty, Chuck Ilik, Ibrahim A. Yung, Philip Yuk Kwong Navarro, Carmen Bolondi, Adriano Kumar, Abhishek Sampath Anania, Chiara Brändl, Björn Meierhofer, David Lupiáñez, Darío G. Müller, Franz-Josef Aktas, Tugce Elsässer, Simon J. Kretzmer, Helene Smith, Zachary D. Meissner, Alexander |
author_facet | Weigert, Raha Hetzel, Sara Bailly, Nina Haggerty, Chuck Ilik, Ibrahim A. Yung, Philip Yuk Kwong Navarro, Carmen Bolondi, Adriano Kumar, Abhishek Sampath Anania, Chiara Brändl, Björn Meierhofer, David Lupiáñez, Darío G. Müller, Franz-Josef Aktas, Tugce Elsässer, Simon J. Kretzmer, Helene Smith, Zachary D. Meissner, Alexander |
author_sort | Weigert, Raha |
collection | PubMed |
description | DNA and Histone 3 Lysine 27 methylation typically function as repressive modifications and operate within distinct genomic compartments. In mammals, the majority of the genome is kept in a DNA methylated state, whereas the Polycomb repressive complexes regulate the unmethylated CpG-rich promoters of developmental genes. In contrast to this general framework, the extra-embryonic lineages display non-canonical, globally intermediate DNA methylation levels, including disruption of local Polycomb domains. Here, to better understand this unusual landscape’s molecular properties, we genetically and chemically perturbed major epigenetic pathways in mouse trophoblast stem cells. We find that the extra-embryonic epigenome reflects ongoing and dynamic de novo methyltransferase recruitment, which is continuously antagonized by Polycomb to maintain intermediate, locally disordered methylation. Despite its disorganized molecular appearance, our data point to a highly controlled equilibrium between counteracting repressors within extra-embryonic cells, one that can seemingly persist indefinitely without bistable features typically seen for embryonic forms of epigenetic regulation. |
format | Online Article Text |
id | pubmed-10104784 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-101047842023-04-16 Dynamic antagonism between key repressive pathways maintains the placental epigenome Weigert, Raha Hetzel, Sara Bailly, Nina Haggerty, Chuck Ilik, Ibrahim A. Yung, Philip Yuk Kwong Navarro, Carmen Bolondi, Adriano Kumar, Abhishek Sampath Anania, Chiara Brändl, Björn Meierhofer, David Lupiáñez, Darío G. Müller, Franz-Josef Aktas, Tugce Elsässer, Simon J. Kretzmer, Helene Smith, Zachary D. Meissner, Alexander Nat Cell Biol Article DNA and Histone 3 Lysine 27 methylation typically function as repressive modifications and operate within distinct genomic compartments. In mammals, the majority of the genome is kept in a DNA methylated state, whereas the Polycomb repressive complexes regulate the unmethylated CpG-rich promoters of developmental genes. In contrast to this general framework, the extra-embryonic lineages display non-canonical, globally intermediate DNA methylation levels, including disruption of local Polycomb domains. Here, to better understand this unusual landscape’s molecular properties, we genetically and chemically perturbed major epigenetic pathways in mouse trophoblast stem cells. We find that the extra-embryonic epigenome reflects ongoing and dynamic de novo methyltransferase recruitment, which is continuously antagonized by Polycomb to maintain intermediate, locally disordered methylation. Despite its disorganized molecular appearance, our data point to a highly controlled equilibrium between counteracting repressors within extra-embryonic cells, one that can seemingly persist indefinitely without bistable features typically seen for embryonic forms of epigenetic regulation. Nature Publishing Group UK 2023-04-06 2023 /pmc/articles/PMC10104784/ /pubmed/37024684 http://dx.doi.org/10.1038/s41556-023-01114-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Weigert, Raha Hetzel, Sara Bailly, Nina Haggerty, Chuck Ilik, Ibrahim A. Yung, Philip Yuk Kwong Navarro, Carmen Bolondi, Adriano Kumar, Abhishek Sampath Anania, Chiara Brändl, Björn Meierhofer, David Lupiáñez, Darío G. Müller, Franz-Josef Aktas, Tugce Elsässer, Simon J. Kretzmer, Helene Smith, Zachary D. Meissner, Alexander Dynamic antagonism between key repressive pathways maintains the placental epigenome |
title | Dynamic antagonism between key repressive pathways maintains the placental epigenome |
title_full | Dynamic antagonism between key repressive pathways maintains the placental epigenome |
title_fullStr | Dynamic antagonism between key repressive pathways maintains the placental epigenome |
title_full_unstemmed | Dynamic antagonism between key repressive pathways maintains the placental epigenome |
title_short | Dynamic antagonism between key repressive pathways maintains the placental epigenome |
title_sort | dynamic antagonism between key repressive pathways maintains the placental epigenome |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10104784/ https://www.ncbi.nlm.nih.gov/pubmed/37024684 http://dx.doi.org/10.1038/s41556-023-01114-y |
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