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Synthetic CpG islands reveal DNA sequence determinants of chromatin structure

The mammalian genome is punctuated by CpG islands (CGIs), which differ sharply from the bulk genome by being rich in G + C and the dinucleotide CpG. CGIs often include transcription initiation sites and display ‘active’ histone marks, notably histone H3 lysine 4 methylation. In embryonic stem cells...

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Autores principales: Wachter, Elisabeth, Quante, Timo, Merusi, Cara, Arczewska, Aleksandra, Stewart, Francis, Webb, Shaun, Bird, Adrian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4204011/
https://www.ncbi.nlm.nih.gov/pubmed/25259796
http://dx.doi.org/10.7554/eLife.03397
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author Wachter, Elisabeth
Quante, Timo
Merusi, Cara
Arczewska, Aleksandra
Stewart, Francis
Webb, Shaun
Bird, Adrian
author_facet Wachter, Elisabeth
Quante, Timo
Merusi, Cara
Arczewska, Aleksandra
Stewart, Francis
Webb, Shaun
Bird, Adrian
author_sort Wachter, Elisabeth
collection PubMed
description The mammalian genome is punctuated by CpG islands (CGIs), which differ sharply from the bulk genome by being rich in G + C and the dinucleotide CpG. CGIs often include transcription initiation sites and display ‘active’ histone marks, notably histone H3 lysine 4 methylation. In embryonic stem cells (ESCs) some CGIs adopt a ‘bivalent’ chromatin state bearing simultaneous ‘active’ and ‘inactive’ chromatin marks. To determine whether CGI chromatin is developmentally programmed at specific genes or is imposed by shared features of CGI DNA, we integrated artificial CGI-like DNA sequences into the ESC genome. We found that bivalency is the default chromatin structure for CpG-rich, G + C-rich DNA. A high CpG density alone is not sufficient for this effect, as A + T-rich sequence settings invariably provoke de novo DNA methylation leading to loss of CGI signature chromatin. We conclude that both CpG-richness and G + C-richness are required for induction of signature chromatin structures at CGIs. DOI: http://dx.doi.org/10.7554/eLife.03397.001
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spelling pubmed-42040112014-11-21 Synthetic CpG islands reveal DNA sequence determinants of chromatin structure Wachter, Elisabeth Quante, Timo Merusi, Cara Arczewska, Aleksandra Stewart, Francis Webb, Shaun Bird, Adrian eLife Genes and Chromosomes The mammalian genome is punctuated by CpG islands (CGIs), which differ sharply from the bulk genome by being rich in G + C and the dinucleotide CpG. CGIs often include transcription initiation sites and display ‘active’ histone marks, notably histone H3 lysine 4 methylation. In embryonic stem cells (ESCs) some CGIs adopt a ‘bivalent’ chromatin state bearing simultaneous ‘active’ and ‘inactive’ chromatin marks. To determine whether CGI chromatin is developmentally programmed at specific genes or is imposed by shared features of CGI DNA, we integrated artificial CGI-like DNA sequences into the ESC genome. We found that bivalency is the default chromatin structure for CpG-rich, G + C-rich DNA. A high CpG density alone is not sufficient for this effect, as A + T-rich sequence settings invariably provoke de novo DNA methylation leading to loss of CGI signature chromatin. We conclude that both CpG-richness and G + C-richness are required for induction of signature chromatin structures at CGIs. DOI: http://dx.doi.org/10.7554/eLife.03397.001 eLife Sciences Publications, Ltd 2014-09-26 /pmc/articles/PMC4204011/ /pubmed/25259796 http://dx.doi.org/10.7554/eLife.03397 Text en Copyright © 2014, Wachter et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Genes and Chromosomes
Wachter, Elisabeth
Quante, Timo
Merusi, Cara
Arczewska, Aleksandra
Stewart, Francis
Webb, Shaun
Bird, Adrian
Synthetic CpG islands reveal DNA sequence determinants of chromatin structure
title Synthetic CpG islands reveal DNA sequence determinants of chromatin structure
title_full Synthetic CpG islands reveal DNA sequence determinants of chromatin structure
title_fullStr Synthetic CpG islands reveal DNA sequence determinants of chromatin structure
title_full_unstemmed Synthetic CpG islands reveal DNA sequence determinants of chromatin structure
title_short Synthetic CpG islands reveal DNA sequence determinants of chromatin structure
title_sort synthetic cpg islands reveal dna sequence determinants of chromatin structure
topic Genes and Chromosomes
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4204011/
https://www.ncbi.nlm.nih.gov/pubmed/25259796
http://dx.doi.org/10.7554/eLife.03397
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