Cargando…

One-Carbon Metabolism Regulates Embryonic Stem Cell Fate Through Epigenetic DNA and Histone Modifications: Implications for Transgenerational Metabolic Disorders in Adults

Human (h) and mouse (m) embryonic stem (ES) cells need specific amino acids to proliferate. mES cells require threonine (Thr) metabolism for epigenetic histone modifications. Thr is converted to glycine and acetyl CoA, and the glycine is metabolized specifically to regulate trimethylation of lysine...

Descripción completa

Detalles Bibliográficos
Autores principales: Van Winkle, Lon J., Ryznar, Rebecca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882271/
https://www.ncbi.nlm.nih.gov/pubmed/31824950
http://dx.doi.org/10.3389/fcell.2019.00300
_version_ 1783474120737947648
author Van Winkle, Lon J.
Ryznar, Rebecca
author_facet Van Winkle, Lon J.
Ryznar, Rebecca
author_sort Van Winkle, Lon J.
collection PubMed
description Human (h) and mouse (m) embryonic stem (ES) cells need specific amino acids to proliferate. mES cells require threonine (Thr) metabolism for epigenetic histone modifications. Thr is converted to glycine and acetyl CoA, and the glycine is metabolized specifically to regulate trimethylation of lysine (Lys) residue 4 in histone H3 (H3K4me3). DNA methylation and methylation of other H3 Lys residues remain unimpaired by Thr deprivation in mES cell culture medium. Similarly, hES cells require methionine (Met) to maintain the Met-SAM (S-adenosyl methionine) cycle of 1-carbon metabolism also for H3K4me3 formation. H3K4me3 is needed specifically to regulate and maintain both mES and hES cell proliferation and their pluripotent states. Better understanding of this regulation is essential since treatment of human diseases and disorders will increasingly involve hES cells. Furthermore, since ES cells are derived from their progenitor cells in preimplantation blastocysts, they serve as models of 1-carbon metabolism in these precursors of all mammalian tissues and organs. One-carbon metabolism challenges, such as a maternal low protein diet (LPD) during preimplantation blastocyst development, contribute to development of metabolic syndrome and related abnormalities in adults. These 1-carbon metabolism challenges result in altered epigenetic DNA and histone modifications in ES progenitor cells and the tissues and organs to which they develop. Moreover, the modified histones could have extracellular as well as intracellular effects, since histones are secreted in uterine fluid and influence early embryo development. Hence, the mechanisms and transgenerational implications of these altered epigenetic DNA and histone modifications warrant concerted further study.
format Online
Article
Text
id pubmed-6882271
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-68822712019-12-10 One-Carbon Metabolism Regulates Embryonic Stem Cell Fate Through Epigenetic DNA and Histone Modifications: Implications for Transgenerational Metabolic Disorders in Adults Van Winkle, Lon J. Ryznar, Rebecca Front Cell Dev Biol Cell and Developmental Biology Human (h) and mouse (m) embryonic stem (ES) cells need specific amino acids to proliferate. mES cells require threonine (Thr) metabolism for epigenetic histone modifications. Thr is converted to glycine and acetyl CoA, and the glycine is metabolized specifically to regulate trimethylation of lysine (Lys) residue 4 in histone H3 (H3K4me3). DNA methylation and methylation of other H3 Lys residues remain unimpaired by Thr deprivation in mES cell culture medium. Similarly, hES cells require methionine (Met) to maintain the Met-SAM (S-adenosyl methionine) cycle of 1-carbon metabolism also for H3K4me3 formation. H3K4me3 is needed specifically to regulate and maintain both mES and hES cell proliferation and their pluripotent states. Better understanding of this regulation is essential since treatment of human diseases and disorders will increasingly involve hES cells. Furthermore, since ES cells are derived from their progenitor cells in preimplantation blastocysts, they serve as models of 1-carbon metabolism in these precursors of all mammalian tissues and organs. One-carbon metabolism challenges, such as a maternal low protein diet (LPD) during preimplantation blastocyst development, contribute to development of metabolic syndrome and related abnormalities in adults. These 1-carbon metabolism challenges result in altered epigenetic DNA and histone modifications in ES progenitor cells and the tissues and organs to which they develop. Moreover, the modified histones could have extracellular as well as intracellular effects, since histones are secreted in uterine fluid and influence early embryo development. Hence, the mechanisms and transgenerational implications of these altered epigenetic DNA and histone modifications warrant concerted further study. Frontiers Media S.A. 2019-11-21 /pmc/articles/PMC6882271/ /pubmed/31824950 http://dx.doi.org/10.3389/fcell.2019.00300 Text en Copyright © 2019 Van Winkle and Ryznar. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Van Winkle, Lon J.
Ryznar, Rebecca
One-Carbon Metabolism Regulates Embryonic Stem Cell Fate Through Epigenetic DNA and Histone Modifications: Implications for Transgenerational Metabolic Disorders in Adults
title One-Carbon Metabolism Regulates Embryonic Stem Cell Fate Through Epigenetic DNA and Histone Modifications: Implications for Transgenerational Metabolic Disorders in Adults
title_full One-Carbon Metabolism Regulates Embryonic Stem Cell Fate Through Epigenetic DNA and Histone Modifications: Implications for Transgenerational Metabolic Disorders in Adults
title_fullStr One-Carbon Metabolism Regulates Embryonic Stem Cell Fate Through Epigenetic DNA and Histone Modifications: Implications for Transgenerational Metabolic Disorders in Adults
title_full_unstemmed One-Carbon Metabolism Regulates Embryonic Stem Cell Fate Through Epigenetic DNA and Histone Modifications: Implications for Transgenerational Metabolic Disorders in Adults
title_short One-Carbon Metabolism Regulates Embryonic Stem Cell Fate Through Epigenetic DNA and Histone Modifications: Implications for Transgenerational Metabolic Disorders in Adults
title_sort one-carbon metabolism regulates embryonic stem cell fate through epigenetic dna and histone modifications: implications for transgenerational metabolic disorders in adults
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882271/
https://www.ncbi.nlm.nih.gov/pubmed/31824950
http://dx.doi.org/10.3389/fcell.2019.00300
work_keys_str_mv AT vanwinklelonj onecarbonmetabolismregulatesembryonicstemcellfatethroughepigeneticdnaandhistonemodificationsimplicationsfortransgenerationalmetabolicdisordersinadults
AT ryznarrebecca onecarbonmetabolismregulatesembryonicstemcellfatethroughepigeneticdnaandhistonemodificationsimplicationsfortransgenerationalmetabolicdisordersinadults