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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2014
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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 |
format | Online Article Text |
id | pubmed-4204011 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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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