Epigenetic conservation at gene regulatory elements revealed by non-methylated DNA profiling in seven vertebrates

Two-thirds of gene promoters in mammals are associated with regions of non-methylated DNA, called CpG islands (CGIs), which counteract the repressive effects of DNA methylation on chromatin. In cold-blooded vertebrates, computational CGI predictions often reside away from gene promoters, suggesting...

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Main Authors:	Hannah K Long, David Sims, Andreas Heger, Neil P Blackledge, Claudia Kutter, Megan L Wright, Frank Grützner, Duncan T Odom, Roger Patient, Chris P Ponting, Robert J Klose
Format:	Article
Language:	English
Published:	eLife Sciences Publications Ltd 2013-02-01
Series:	eLife
Subjects:	CpG island DNA methylation epigenetic Chromatin Evolutionary conservation
Online Access:	https://elifesciences.org/articles/00348

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spelling	doaj-8f9b32865ca8491b8fcd154f9776e7012021-05-04T21:29:07ZengeLife Sciences Publications LtdeLife2050-084X2013-02-01210.7554/eLife.00348Epigenetic conservation at gene regulatory elements revealed by non-methylated DNA profiling in seven vertebratesHannah K Long0David Sims1Andreas Heger2Neil P Blackledge3Claudia Kutter4Megan L Wright5Frank Grützner6Duncan T Odom7Roger Patient8Chris P Ponting9Robert J Klose10Department of Biochemistry, University of Oxford, Oxford, United Kingdom; Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United KingdomCGAT, MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United KingdomCGAT, MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United KingdomDepartment of Biochemistry, University of Oxford, Oxford, United KingdomCancer Research UK – Cambridge Institute, University of Cambridge, Cambridge, United KingdomSchool of Molecular and Biomedical Science, The Robinson Institute, University of Adelaide, Adelaide, AustraliaSchool of Molecular and Biomedical Science, The Robinson Institute, University of Adelaide, Adelaide, AustraliaCancer Research UK – Cambridge Institute, University of Cambridge, Cambridge, United Kingdom; Wellcome Trust Sanger Institute, Cambridge, United KingdomWeatherall Institute of Molecular Medicine, University of Oxford, Oxford, United KingdomCGAT, MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United KingdomDepartment of Biochemistry, University of Oxford, Oxford, United KingdomTwo-thirds of gene promoters in mammals are associated with regions of non-methylated DNA, called CpG islands (CGIs), which counteract the repressive effects of DNA methylation on chromatin. In cold-blooded vertebrates, computational CGI predictions often reside away from gene promoters, suggesting a major divergence in gene promoter architecture across vertebrates. By experimentally identifying non-methylated DNA in the genomes of seven diverse vertebrates, we instead reveal that non-methylated islands (NMIs) of DNA are a central feature of vertebrate gene promoters. Furthermore, NMIs are present at orthologous genes across vast evolutionary distances, revealing a surprising level of conservation in this epigenetic feature. By profiling NMIs in different tissues and developmental stages we uncover a unifying set of features that are central to the function of NMIs in vertebrates. Together these findings demonstrate an ancient logic for NMI usage at gene promoters and reveal an unprecedented level of epigenetic conservation across vertebrate evolution.https://elifesciences.org/articles/00348CpG islandDNA methylationepigeneticChromatinEvolutionary conservation
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Hannah K Long David Sims Andreas Heger Neil P Blackledge Claudia Kutter Megan L Wright Frank Grützner Duncan T Odom Roger Patient Chris P Ponting Robert J Klose
spellingShingle	Hannah K Long David Sims Andreas Heger Neil P Blackledge Claudia Kutter Megan L Wright Frank Grützner Duncan T Odom Roger Patient Chris P Ponting Robert J Klose Epigenetic conservation at gene regulatory elements revealed by non-methylated DNA profiling in seven vertebrates eLife CpG island DNA methylation epigenetic Chromatin Evolutionary conservation
author_facet	Hannah K Long David Sims Andreas Heger Neil P Blackledge Claudia Kutter Megan L Wright Frank Grützner Duncan T Odom Roger Patient Chris P Ponting Robert J Klose
author_sort	Hannah K Long
title	Epigenetic conservation at gene regulatory elements revealed by non-methylated DNA profiling in seven vertebrates
title_short	Epigenetic conservation at gene regulatory elements revealed by non-methylated DNA profiling in seven vertebrates
title_full	Epigenetic conservation at gene regulatory elements revealed by non-methylated DNA profiling in seven vertebrates
title_fullStr	Epigenetic conservation at gene regulatory elements revealed by non-methylated DNA profiling in seven vertebrates
title_full_unstemmed	Epigenetic conservation at gene regulatory elements revealed by non-methylated DNA profiling in seven vertebrates
title_sort	epigenetic conservation at gene regulatory elements revealed by non-methylated dna profiling in seven vertebrates
publisher	eLife Sciences Publications Ltd
series	eLife
issn	2050-084X
publishDate	2013-02-01
description	Two-thirds of gene promoters in mammals are associated with regions of non-methylated DNA, called CpG islands (CGIs), which counteract the repressive effects of DNA methylation on chromatin. In cold-blooded vertebrates, computational CGI predictions often reside away from gene promoters, suggesting a major divergence in gene promoter architecture across vertebrates. By experimentally identifying non-methylated DNA in the genomes of seven diverse vertebrates, we instead reveal that non-methylated islands (NMIs) of DNA are a central feature of vertebrate gene promoters. Furthermore, NMIs are present at orthologous genes across vast evolutionary distances, revealing a surprising level of conservation in this epigenetic feature. By profiling NMIs in different tissues and developmental stages we uncover a unifying set of features that are central to the function of NMIs in vertebrates. Together these findings demonstrate an ancient logic for NMI usage at gene promoters and reveal an unprecedented level of epigenetic conservation across vertebrate evolution.
topic	CpG island DNA methylation epigenetic Chromatin Evolutionary conservation
url	https://elifesciences.org/articles/00348
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Epigenetic conservation at gene regulatory elements revealed by non-methylated DNA profiling in seven vertebrates

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