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Human epigenome project--up and running.

Bradbury J - PLoS Biol. (2003)

View Article: PubMed Central - PubMed

Affiliation: janeb@sciscribe.u-net.com <janeb@sciscribe.u-net.com>

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But what is an epigenome, and why have the Wellcome Trust Sanger Institute (Hinxton, United Kingdom) and Epigenomics AG (Berlin, Germany) recently announced the launch of the Human Epigenome Project (HEP), a five-year undertaking during which DNA methylation sites throughout the human genome will be mapped? The HEP is the brainchild of immunogeneticist Stephan Beck of the Sanger Institute and Alexander Olek, chief executive officer of Epigenomics AG... The Human Genome Project … ‘provided the blueprint for life, but the epigenome will tell us how this whole thing gets executed’... That ‘something else’ is chemical modifications of genes that are heritable from one cell generation to the next and that affect gene expression but do not alter the DNA sequence... For individual cells, this code on top of a code helps to determine whether a cell is a blood cell, a fat cell, or something else... And in the case of monozygotic twins, unexpected differences may result from chance variations in this superimposed code (Box 1)... In October 2000, the Human Epigenome Consortium (the Sanger Institute, Epigenomics AG, and the Centre National de Génotypage in Evry, France) started a European Union-funded pilot project to map the methylation sites within the major histocompatibility complex (MHC) region in seven different human tissues... The promoter regions are the places where the elements that control gene expression are often located, and DNA methylation occurs at cytosine residues within CpG motifs, hence the choice of CpG-rich regions... The methylation status of more than 100, 000 sites was determined during the three-year pilot study and the results analysed to show where there were methylation differences in the MHC between different tissues (Figure 2). ‘We found major methylation differences between loci and between tissues’, says Beck, ‘and we are particularly interested in what we call methylation variable positions (MVPs), which we believe will advance our ability to understand and diagnose human disease’... Sample preparation and amplification will be done at Epigenomics AG, the Sanger Institute will do the sequencing and raw data analysis, and then the data will be jointly evaluated and mined, ‘a huge collaborative experiment’, says Olek... The Wellcome Trust and Epigenomics AG are jointly funding phase I of the HEP, thus avoiding a rerun of the situation that occurred in the Human Genome Project, in which a commercial company and a public effort ended up competing with each other... Reik suggests that this could indicate that epigenetic reprogramming—the process needed to turn a somatic cell back into a totipotent cell—is very inefficient. ‘We have some evidence that there is a link between the success of epigenetic reprogramming and that of cloning, and we really have to understand the reprogramming process to get reproductive cloning to work', says Reik. ‘At the moment the whole process is a black box’... Because of this, many scientists argue that human reproductive cloning, leaving aside the ethical concerns about it, simply isn't a safe option at present, a concern reflected in the recent call by 60 scientific academies for a ban on its development... A far cry from the situation 10 years ago, says Reik, ‘when the field had the smell of something esoteric that no one really understood and whose significance was not clear... Now it is one of the mainstream exciting areas of post-genomic biology’, he concludes, and one which will hopefully yield to the might of large consortia like the Epigenome Network and the HEP.

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Example of HEP Methylation Data for the BAT8 Gene, an MHC-Linked Histone MethyltransferaseIn this case, two regions marked in red were analysed in 31 samples (rows) from seven tissues (blocks of rows). The predicted structure of the gene is shown below with coloured boxes indicating the exons. As part of the launch of the HEP on October 7, 2003, these data and others, together with experimental details of the pilot study, were released at www.epigenome.org.
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pbio.0000082-g002: Example of HEP Methylation Data for the BAT8 Gene, an MHC-Linked Histone MethyltransferaseIn this case, two regions marked in red were analysed in 31 samples (rows) from seven tissues (blocks of rows). The predicted structure of the gene is shown below with coloured boxes indicating the exons. As part of the launch of the HEP on October 7, 2003, these data and others, together with experimental details of the pilot study, were released at www.epigenome.org.

Mentions: The methylation status of more than 100, 000 sites was determined during the three-year pilot study and the results analysed to show where there were methylation differences in the MHC between different tissues (Figure 2). ‘We found major methylation differences between loci and between tissues’, says Beck, ‘and we are particularly interested in what we call methylation variable positions (MVPs), which we believe will advance our ability to understand and diagnose human disease’. Olek echoes Beck's satisfaction with the results to date. ‘We can see that there is hidden treasure in the data that needs mining, and that treasure is obviously going to get much bigger when we sequence the whole thing’, he says.


Human epigenome project--up and running.

Bradbury J - PLoS Biol. (2003)

Example of HEP Methylation Data for the BAT8 Gene, an MHC-Linked Histone MethyltransferaseIn this case, two regions marked in red were analysed in 31 samples (rows) from seven tissues (blocks of rows). The predicted structure of the gene is shown below with coloured boxes indicating the exons. As part of the launch of the HEP on October 7, 2003, these data and others, together with experimental details of the pilot study, were released at www.epigenome.org.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC300691&req=5

pbio.0000082-g002: Example of HEP Methylation Data for the BAT8 Gene, an MHC-Linked Histone MethyltransferaseIn this case, two regions marked in red were analysed in 31 samples (rows) from seven tissues (blocks of rows). The predicted structure of the gene is shown below with coloured boxes indicating the exons. As part of the launch of the HEP on October 7, 2003, these data and others, together with experimental details of the pilot study, were released at www.epigenome.org.
Mentions: The methylation status of more than 100, 000 sites was determined during the three-year pilot study and the results analysed to show where there were methylation differences in the MHC between different tissues (Figure 2). ‘We found major methylation differences between loci and between tissues’, says Beck, ‘and we are particularly interested in what we call methylation variable positions (MVPs), which we believe will advance our ability to understand and diagnose human disease’. Olek echoes Beck's satisfaction with the results to date. ‘We can see that there is hidden treasure in the data that needs mining, and that treasure is obviously going to get much bigger when we sequence the whole thing’, he says.

View Article: PubMed Central - PubMed

Affiliation: janeb@sciscribe.u-net.com <janeb@sciscribe.u-net.com>

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

But what is an epigenome, and why have the Wellcome Trust Sanger Institute (Hinxton, United Kingdom) and Epigenomics AG (Berlin, Germany) recently announced the launch of the Human Epigenome Project (HEP), a five-year undertaking during which DNA methylation sites throughout the human genome will be mapped? The HEP is the brainchild of immunogeneticist Stephan Beck of the Sanger Institute and Alexander Olek, chief executive officer of Epigenomics AG... The Human Genome Project … ‘provided the blueprint for life, but the epigenome will tell us how this whole thing gets executed’... That ‘something else’ is chemical modifications of genes that are heritable from one cell generation to the next and that affect gene expression but do not alter the DNA sequence... For individual cells, this code on top of a code helps to determine whether a cell is a blood cell, a fat cell, or something else... And in the case of monozygotic twins, unexpected differences may result from chance variations in this superimposed code (Box 1)... In October 2000, the Human Epigenome Consortium (the Sanger Institute, Epigenomics AG, and the Centre National de Génotypage in Evry, France) started a European Union-funded pilot project to map the methylation sites within the major histocompatibility complex (MHC) region in seven different human tissues... The promoter regions are the places where the elements that control gene expression are often located, and DNA methylation occurs at cytosine residues within CpG motifs, hence the choice of CpG-rich regions... The methylation status of more than 100, 000 sites was determined during the three-year pilot study and the results analysed to show where there were methylation differences in the MHC between different tissues (Figure 2). ‘We found major methylation differences between loci and between tissues’, says Beck, ‘and we are particularly interested in what we call methylation variable positions (MVPs), which we believe will advance our ability to understand and diagnose human disease’... Sample preparation and amplification will be done at Epigenomics AG, the Sanger Institute will do the sequencing and raw data analysis, and then the data will be jointly evaluated and mined, ‘a huge collaborative experiment’, says Olek... The Wellcome Trust and Epigenomics AG are jointly funding phase I of the HEP, thus avoiding a rerun of the situation that occurred in the Human Genome Project, in which a commercial company and a public effort ended up competing with each other... Reik suggests that this could indicate that epigenetic reprogramming—the process needed to turn a somatic cell back into a totipotent cell—is very inefficient. ‘We have some evidence that there is a link between the success of epigenetic reprogramming and that of cloning, and we really have to understand the reprogramming process to get reproductive cloning to work', says Reik. ‘At the moment the whole process is a black box’... Because of this, many scientists argue that human reproductive cloning, leaving aside the ethical concerns about it, simply isn't a safe option at present, a concern reflected in the recent call by 60 scientific academies for a ban on its development... A far cry from the situation 10 years ago, says Reik, ‘when the field had the smell of something esoteric that no one really understood and whose significance was not clear... Now it is one of the mainstream exciting areas of post-genomic biology’, he concludes, and one which will hopefully yield to the might of large consortia like the Epigenome Network and the HEP.

Show MeSH