- Feb 8, 2001
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Genetic switches discovery could mean lights out on cancer
Genetic switches discovery could mean lights out on cancer
By Wai Lang Chu
LATEST NEWS HEADLINES
* Strong growth seen in US for barrier plastic packaging
* GMP an unnecessary burden for excipients, review concludes
* Pharma: why the wandering eye towards emerging markets?
* Alloga expands logistics territory
* Preclinical services news in brief
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* EMBL
* epigenetics
* DNA methylation
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12-Mar-2008 - European researchers think they may have found a series of DNA switches that control which genes are switched on and when, giving rise to a new research direction that may shed new light on the molecular basis of cancer and development.
The discovery involves a process known as methylation, in which a chemical residue called a methyl group is attached to parts of the DNA. The methyl group causes the gene to shut down preventing the protein production process.
Researchers at the European Molecular Biology Laboratory in Heidelberg in Germany previously believed that in the chemical process of methylation a gene was stable and unchangeable.
Ongoing investigations uncovered a series of mechanisms that questioned this belief as they demonstrated the methylation process was transient, cyclical and dynamic. This insight came from an approach of synchronising all cells in a population such that variations were made visible.
Using breast cancer cells, the scientists established that when oestrogen was withdrawn from the cell culture, or if the cells are treated with the anticancer drug doxorubicin, the methyl groups are removed from the regulatory regions of certain genes within minutes.
With the methyl groups gone, the genes became active, before remethylation shut them down again. This process appeared cyclical, repeating itself every one and a half hours.
"We assumed for a long time that methylation can act on a very short timescale. The results challenge our understanding of epigenetics as a means to regulate gene expression permanently," says Sara Kangaspeska, who carried out the research along with Brenda Stride.
Epigenetic changes to the structure of chromatin (tightly packaged DNA), grant or deny access to the molecular machinery that transcribes DNA and thereby regulate gene expression.
"In particular breast cancer is affected by oestrogen signalling and changes in epigenetic control," commented George Reid, co-senior author of the study. "Our next step will be to find small molecules that target the cyclical methylation processes to clarify their precise role."
The new findings significantly impact upon current understanding of how cells interpret their DNA as the research suggests epigenetic regulation can affect gene expression in the immediate and long-term.
Coupled with the sequencing of the human genome the public has become well aware of the impact DNA has in the origin and progression of disease.
Crucially, only some of the total possibilities of genes are expressed in any given tissue. For example, a protein that is active in a nerve cell is not expressed in the liver. The way in which this is controlled is a complex area of which this latest research has opened up new avenues.
As well as cancer, the discovery has implications for inherited diseases such as Downs syndrome. A woman with two chromosomes has one of these silenced by the same methylation tag so there is only one active X chromosome. The consequence of an excess level of expression can result in Downs syndrome where an extra chromosome is active.
Genetic switches discovery could mean lights out on cancer
By Wai Lang Chu
LATEST NEWS HEADLINES
* Strong growth seen in US for barrier plastic packaging
* GMP an unnecessary burden for excipients, review concludes
* Pharma: why the wandering eye towards emerging markets?
* Alloga expands logistics territory
* Preclinical services news in brief
GET THE LATEST MARKET REPORTS
* EMBL
* epigenetics
* DNA methylation
All market reports
12-Mar-2008 - European researchers think they may have found a series of DNA switches that control which genes are switched on and when, giving rise to a new research direction that may shed new light on the molecular basis of cancer and development.
The discovery involves a process known as methylation, in which a chemical residue called a methyl group is attached to parts of the DNA. The methyl group causes the gene to shut down preventing the protein production process.
Researchers at the European Molecular Biology Laboratory in Heidelberg in Germany previously believed that in the chemical process of methylation a gene was stable and unchangeable.
Ongoing investigations uncovered a series of mechanisms that questioned this belief as they demonstrated the methylation process was transient, cyclical and dynamic. This insight came from an approach of synchronising all cells in a population such that variations were made visible.
Using breast cancer cells, the scientists established that when oestrogen was withdrawn from the cell culture, or if the cells are treated with the anticancer drug doxorubicin, the methyl groups are removed from the regulatory regions of certain genes within minutes.
With the methyl groups gone, the genes became active, before remethylation shut them down again. This process appeared cyclical, repeating itself every one and a half hours.
"We assumed for a long time that methylation can act on a very short timescale. The results challenge our understanding of epigenetics as a means to regulate gene expression permanently," says Sara Kangaspeska, who carried out the research along with Brenda Stride.
Epigenetic changes to the structure of chromatin (tightly packaged DNA), grant or deny access to the molecular machinery that transcribes DNA and thereby regulate gene expression.
"In particular breast cancer is affected by oestrogen signalling and changes in epigenetic control," commented George Reid, co-senior author of the study. "Our next step will be to find small molecules that target the cyclical methylation processes to clarify their precise role."
The new findings significantly impact upon current understanding of how cells interpret their DNA as the research suggests epigenetic regulation can affect gene expression in the immediate and long-term.
Coupled with the sequencing of the human genome the public has become well aware of the impact DNA has in the origin and progression of disease.
Crucially, only some of the total possibilities of genes are expressed in any given tissue. For example, a protein that is active in a nerve cell is not expressed in the liver. The way in which this is controlled is a complex area of which this latest research has opened up new avenues.
As well as cancer, the discovery has implications for inherited diseases such as Downs syndrome. A woman with two chromosomes has one of these silenced by the same methylation tag so there is only one active X chromosome. The consequence of an excess level of expression can result in Downs syndrome where an extra chromosome is active.
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