Targeting of de novo DNA methylation throughout the Oct-4 gene regulatory region in differentiating embryonic stem cells.

Differentiation of embryonic stem (ES) cells is accompanied by silencing of the Oct-4 gene and de novo DNA methylation of its regulatory region. Previous studies have focused on the requirements for promoter region methylation. We therefore undertook to analyse the progression of DNA methylation of...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Rodoniki Athanasiadou, Dina de Sousa, Kevin Myant, Cara Merusi, Irina Stancheva, Adrian Bird
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/953033e4ec004449b1692e08e8a028a1
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:953033e4ec004449b1692e08e8a028a1
record_format	dspace
spelling	oai:doaj.org-article:953033e4ec004449b1692e08e8a028a12021-11-25T06:24:51ZTargeting of de novo DNA methylation throughout the Oct-4 gene regulatory region in differentiating embryonic stem cells.1932-620310.1371/journal.pone.0009937https://doaj.org/article/953033e4ec004449b1692e08e8a028a12010-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20376339/?tool=EBIhttps://doaj.org/toc/1932-6203Differentiation of embryonic stem (ES) cells is accompanied by silencing of the Oct-4 gene and de novo DNA methylation of its regulatory region. Previous studies have focused on the requirements for promoter region methylation. We therefore undertook to analyse the progression of DNA methylation of the approximately 2000 base pair regulatory region of Oct-4 in ES cells that are wildtype or deficient for key proteins. We find that de novo methylation is initially seeded at two discrete sites, the proximal enhancer and distal promoter, spreading later to neighboring regions, including the remainder of the promoter. De novo methyltransferases Dnmt3a and Dnmt3b cooperate in the initial targeted stage of de novo methylation. Efficient completion of the pattern requires Dnmt3a and Dnmt1, but not Dnmt3b. Methylation of the Oct-4 promoter depends on the histone H3 lysine 9 methyltransferase G9a, as shown previously, but CpG methylation throughout most of the regulatory region accumulates even in the absence of G9a. Analysis of the Oct-4 regulatory domain as a whole has allowed us to detect targeted de novo methylation and to refine our understanding the roles of key protein components in this process.Rodoniki AthanasiadouDina de SousaKevin MyantCara MerusiIrina StanchevaAdrian BirdPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 4, p e9937 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rodoniki Athanasiadou Dina de Sousa Kevin Myant Cara Merusi Irina Stancheva Adrian Bird Targeting of de novo DNA methylation throughout the Oct-4 gene regulatory region in differentiating embryonic stem cells.
description	Differentiation of embryonic stem (ES) cells is accompanied by silencing of the Oct-4 gene and de novo DNA methylation of its regulatory region. Previous studies have focused on the requirements for promoter region methylation. We therefore undertook to analyse the progression of DNA methylation of the approximately 2000 base pair regulatory region of Oct-4 in ES cells that are wildtype or deficient for key proteins. We find that de novo methylation is initially seeded at two discrete sites, the proximal enhancer and distal promoter, spreading later to neighboring regions, including the remainder of the promoter. De novo methyltransferases Dnmt3a and Dnmt3b cooperate in the initial targeted stage of de novo methylation. Efficient completion of the pattern requires Dnmt3a and Dnmt1, but not Dnmt3b. Methylation of the Oct-4 promoter depends on the histone H3 lysine 9 methyltransferase G9a, as shown previously, but CpG methylation throughout most of the regulatory region accumulates even in the absence of G9a. Analysis of the Oct-4 regulatory domain as a whole has allowed us to detect targeted de novo methylation and to refine our understanding the roles of key protein components in this process.
format	article
author	Rodoniki Athanasiadou Dina de Sousa Kevin Myant Cara Merusi Irina Stancheva Adrian Bird
author_facet	Rodoniki Athanasiadou Dina de Sousa Kevin Myant Cara Merusi Irina Stancheva Adrian Bird
author_sort	Rodoniki Athanasiadou
title	Targeting of de novo DNA methylation throughout the Oct-4 gene regulatory region in differentiating embryonic stem cells.
title_short	Targeting of de novo DNA methylation throughout the Oct-4 gene regulatory region in differentiating embryonic stem cells.
title_full	Targeting of de novo DNA methylation throughout the Oct-4 gene regulatory region in differentiating embryonic stem cells.
title_fullStr	Targeting of de novo DNA methylation throughout the Oct-4 gene regulatory region in differentiating embryonic stem cells.
title_full_unstemmed	Targeting of de novo DNA methylation throughout the Oct-4 gene regulatory region in differentiating embryonic stem cells.
title_sort	targeting of de novo dna methylation throughout the oct-4 gene regulatory region in differentiating embryonic stem cells.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/953033e4ec004449b1692e08e8a028a1
work_keys_str_mv	AT rodonikiathanasiadou targetingofdenovodnamethylationthroughouttheoct4generegulatoryregionindifferentiatingembryonicstemcells AT dinadesousa targetingofdenovodnamethylationthroughouttheoct4generegulatoryregionindifferentiatingembryonicstemcells AT kevinmyant targetingofdenovodnamethylationthroughouttheoct4generegulatoryregionindifferentiatingembryonicstemcells AT caramerusi targetingofdenovodnamethylationthroughouttheoct4generegulatoryregionindifferentiatingembryonicstemcells AT irinastancheva targetingofdenovodnamethylationthroughouttheoct4generegulatoryregionindifferentiatingembryonicstemcells AT adrianbird targetingofdenovodnamethylationthroughouttheoct4generegulatoryregionindifferentiatingembryonicstemcells
_version_	1718413758099881984

Targeting of de novo DNA methylation throughout the Oct-4 gene regulatory region in differentiating embryonic stem cells.

Ejemplares similares