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SUV4-20 activity in the preimplantation mouse embryo controls timely replication

Extensive chromatin remodeling after fertilization is thought to take place to allow a new developmental program to start. This includes dynamic changes in histone methylation and, in particular, the remodeling of constitutive heterochromatic marks such as histone H4 Lys20 trimethylation (H4K20me3)....

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Autores principales: Eid, André, Rodriguez-Terrones, Diego, Burton, Adam, Torres-Padilla, Maria-Elena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5159666/
https://www.ncbi.nlm.nih.gov/pubmed/27920088
http://dx.doi.org/10.1101/gad.288969.116
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author Eid, André
Rodriguez-Terrones, Diego
Burton, Adam
Torres-Padilla, Maria-Elena
author_facet Eid, André
Rodriguez-Terrones, Diego
Burton, Adam
Torres-Padilla, Maria-Elena
author_sort Eid, André
collection PubMed
description Extensive chromatin remodeling after fertilization is thought to take place to allow a new developmental program to start. This includes dynamic changes in histone methylation and, in particular, the remodeling of constitutive heterochromatic marks such as histone H4 Lys20 trimethylation (H4K20me3). While the essential function of H4K20me1 in preimplantation mouse embryos is well established, the role of the additional H4K20 methylation states through the action of the SUV4-20 methyltransferases has not been addressed. Here we show that Suv4-20h1/h2 are mostly absent in mouse embryos before implantation, underscoring a rapid decrease of H4K20me3 from the two-cell stage onward. We addressed the functional significance of this remodeling by introducing Suv4-20h1 and Suv4-20h2 in early embryos. Ectopic expression of Suv4-20h2 leads to sustained levels of H4K20me3, developmental arrest, and defects in S-phase progression. The developmental phenotype can be partially overcome through inhibition of the ATR pathway, suggesting that the main function for the remodeling of H4K20me3 after fertilization is to allow the timely and coordinated progression of replication. This is in contrast to the replication program in somatic cells, where H4K20me3 has been shown to promote replication origin licensing, and anticipates a different regulation of replication during this early developmental time window.
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spelling pubmed-51596662017-05-15 SUV4-20 activity in the preimplantation mouse embryo controls timely replication Eid, André Rodriguez-Terrones, Diego Burton, Adam Torres-Padilla, Maria-Elena Genes Dev Research Paper Extensive chromatin remodeling after fertilization is thought to take place to allow a new developmental program to start. This includes dynamic changes in histone methylation and, in particular, the remodeling of constitutive heterochromatic marks such as histone H4 Lys20 trimethylation (H4K20me3). While the essential function of H4K20me1 in preimplantation mouse embryos is well established, the role of the additional H4K20 methylation states through the action of the SUV4-20 methyltransferases has not been addressed. Here we show that Suv4-20h1/h2 are mostly absent in mouse embryos before implantation, underscoring a rapid decrease of H4K20me3 from the two-cell stage onward. We addressed the functional significance of this remodeling by introducing Suv4-20h1 and Suv4-20h2 in early embryos. Ectopic expression of Suv4-20h2 leads to sustained levels of H4K20me3, developmental arrest, and defects in S-phase progression. The developmental phenotype can be partially overcome through inhibition of the ATR pathway, suggesting that the main function for the remodeling of H4K20me3 after fertilization is to allow the timely and coordinated progression of replication. This is in contrast to the replication program in somatic cells, where H4K20me3 has been shown to promote replication origin licensing, and anticipates a different regulation of replication during this early developmental time window. Cold Spring Harbor Laboratory Press 2016-11-15 /pmc/articles/PMC5159666/ /pubmed/27920088 http://dx.doi.org/10.1101/gad.288969.116 Text en © 2016 Eid et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Paper
Eid, André
Rodriguez-Terrones, Diego
Burton, Adam
Torres-Padilla, Maria-Elena
SUV4-20 activity in the preimplantation mouse embryo controls timely replication
title SUV4-20 activity in the preimplantation mouse embryo controls timely replication
title_full SUV4-20 activity in the preimplantation mouse embryo controls timely replication
title_fullStr SUV4-20 activity in the preimplantation mouse embryo controls timely replication
title_full_unstemmed SUV4-20 activity in the preimplantation mouse embryo controls timely replication
title_short SUV4-20 activity in the preimplantation mouse embryo controls timely replication
title_sort suv4-20 activity in the preimplantation mouse embryo controls timely replication
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5159666/
https://www.ncbi.nlm.nih.gov/pubmed/27920088
http://dx.doi.org/10.1101/gad.288969.116
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