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DNA Methylation Profiling of Embryonic Stem Cell Differentiation into the Three Germ Layers

Embryogenesis is tightly regulated by multiple levels of epigenetic regulation such as DNA methylation, histone modification, and chromatin remodeling. DNA methylation patterns are erased in primordial germ cells and in the interval immediately following fertilization. Subsequent developmental repro...

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Autores principales: Isagawa, Takayuki, Nagae, Genta, Shiraki, Nobuaki, Fujita, Takanori, Sato, Noriko, Ishikawa, Shumpei, Kume, Shoen, Aburatani, Hiroyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189249/
https://www.ncbi.nlm.nih.gov/pubmed/22016810
http://dx.doi.org/10.1371/journal.pone.0026052
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author Isagawa, Takayuki
Nagae, Genta
Shiraki, Nobuaki
Fujita, Takanori
Sato, Noriko
Ishikawa, Shumpei
Kume, Shoen
Aburatani, Hiroyuki
author_facet Isagawa, Takayuki
Nagae, Genta
Shiraki, Nobuaki
Fujita, Takanori
Sato, Noriko
Ishikawa, Shumpei
Kume, Shoen
Aburatani, Hiroyuki
author_sort Isagawa, Takayuki
collection PubMed
description Embryogenesis is tightly regulated by multiple levels of epigenetic regulation such as DNA methylation, histone modification, and chromatin remodeling. DNA methylation patterns are erased in primordial germ cells and in the interval immediately following fertilization. Subsequent developmental reprogramming occurs by de novo methylation and demethylation. Variance in DNA methylation patterns between different cell types is not well understood. Here, using methylated DNA immunoprecipitation and tiling array technology, we have comprehensively analyzed DNA methylation patterns at proximal promoter regions in mouse embryonic stem (ES) cells, ES cell-derived early germ layers (ectoderm, endoderm and mesoderm) and four adult tissues (brain, liver, skeletal muscle and sperm). Most of the methylated regions are methylated across all three germ layers and in the three adult somatic tissues. This commonly methylated gene set is enriched in germ cell-associated genes that are generally transcriptionally inactive in somatic cells. We also compared DNA methylation patterns by global mapping of histone H3 lysine 4/27 trimethylation, and found that gain of DNA methylation correlates with loss of histone H3 lysine 4 trimethylation. Our combined findings indicate that differentiation of ES cells into the three germ layers is accompanied by an increased number of commonly methylated DNA regions and that these tissue-specific alterations in methylation occur for only a small number of genes. DNA methylation at the proximal promoter regions of commonly methylated genes thus appears to be an irreversible mark which functions to fix somatic lineage by repressing the transcription of germ cell-specific genes.
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spelling pubmed-31892492011-10-20 DNA Methylation Profiling of Embryonic Stem Cell Differentiation into the Three Germ Layers Isagawa, Takayuki Nagae, Genta Shiraki, Nobuaki Fujita, Takanori Sato, Noriko Ishikawa, Shumpei Kume, Shoen Aburatani, Hiroyuki PLoS One Research Article Embryogenesis is tightly regulated by multiple levels of epigenetic regulation such as DNA methylation, histone modification, and chromatin remodeling. DNA methylation patterns are erased in primordial germ cells and in the interval immediately following fertilization. Subsequent developmental reprogramming occurs by de novo methylation and demethylation. Variance in DNA methylation patterns between different cell types is not well understood. Here, using methylated DNA immunoprecipitation and tiling array technology, we have comprehensively analyzed DNA methylation patterns at proximal promoter regions in mouse embryonic stem (ES) cells, ES cell-derived early germ layers (ectoderm, endoderm and mesoderm) and four adult tissues (brain, liver, skeletal muscle and sperm). Most of the methylated regions are methylated across all three germ layers and in the three adult somatic tissues. This commonly methylated gene set is enriched in germ cell-associated genes that are generally transcriptionally inactive in somatic cells. We also compared DNA methylation patterns by global mapping of histone H3 lysine 4/27 trimethylation, and found that gain of DNA methylation correlates with loss of histone H3 lysine 4 trimethylation. Our combined findings indicate that differentiation of ES cells into the three germ layers is accompanied by an increased number of commonly methylated DNA regions and that these tissue-specific alterations in methylation occur for only a small number of genes. DNA methylation at the proximal promoter regions of commonly methylated genes thus appears to be an irreversible mark which functions to fix somatic lineage by repressing the transcription of germ cell-specific genes. Public Library of Science 2011-10-07 /pmc/articles/PMC3189249/ /pubmed/22016810 http://dx.doi.org/10.1371/journal.pone.0026052 Text en Isagawa et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Isagawa, Takayuki
Nagae, Genta
Shiraki, Nobuaki
Fujita, Takanori
Sato, Noriko
Ishikawa, Shumpei
Kume, Shoen
Aburatani, Hiroyuki
DNA Methylation Profiling of Embryonic Stem Cell Differentiation into the Three Germ Layers
title DNA Methylation Profiling of Embryonic Stem Cell Differentiation into the Three Germ Layers
title_full DNA Methylation Profiling of Embryonic Stem Cell Differentiation into the Three Germ Layers
title_fullStr DNA Methylation Profiling of Embryonic Stem Cell Differentiation into the Three Germ Layers
title_full_unstemmed DNA Methylation Profiling of Embryonic Stem Cell Differentiation into the Three Germ Layers
title_short DNA Methylation Profiling of Embryonic Stem Cell Differentiation into the Three Germ Layers
title_sort dna methylation profiling of embryonic stem cell differentiation into the three germ layers
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189249/
https://www.ncbi.nlm.nih.gov/pubmed/22016810
http://dx.doi.org/10.1371/journal.pone.0026052
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