September 25, 2006
Faster Method To Read Epigenetic Information Tested

Methyl groups (a carbon and 3 hydrogens attached to a larger molecule) get placed on outsides of DNA double helixes in order to control gene expression. A group of scientists has found that embryonic cell type have unqiue patterns of methyl group attachment (methylation) that make them different from other cell types.

San Diego, Calif. -- Scientists from the Burnham Institute for Medical Research (BIMR) and Illumina Inc., in collaboration with stem cell researchers around the world, have found that the DNA of human embryonic stem cells is chemically modified in a characteristic, predictable pattern. This pattern distinguishes human embryonic stem cells from normal adult cells and cell lines, including cancer cells. The study, which appears online today in Genome Research, should help researchers understand how epigenetic factors contribute to self-renewal and developmental pluripotence, unique characteristics of human embryonic stem cells that may one day allow them to be used to replace diseased or damaged cells with healthy ones in a process called therapeutic cloning.

Embryonic stem cells are derived from embryos that are undergoing a period of intense cellular activity, including the chemical addition of methyl groups to specific DNA sequences in a process known as DNA methylation. The methylation and demethylation of particular DNA sequences in the genome are known to have profound effects on cellular behavior and differentiation. For example, DNA methylation is one of the critical epigenetic events leading to the inactivation of one X chromosome in female cells. Failure to establish a normal pattern of DNA methylation during embryogenesis can cause immunological deficiencies, mental retardation and other abnormalities such as Rett, Prader-Willi, Angelman and Beckwith-Wiedemann syndromes.

This result is entirely unsurprising. Methylation is an expected way that cells get controlled to act like one cell type rather than other cell types. For example, methyl groups can prevent proteins from binding to a section of DNA and thereby prevent cellular machnery from reading specific genes that have been methylated.

The way more exciting result here is the development of technology for measuring methylation of hundreds of sites on DNA at a time.

Until recently, DNA methylation could only be studied one gene at a time. But a new microarray-based technique developed at Illumina enabled the scientists conducting this new study to simultaneously examine hundreds of potential methylation sites, thereby revealing global patterns. "Analyzing the DNA methylation pattern of hundreds of genes at a time opens a new window for epigenetic research," says Dr. Jian-Bing Fan, director of molecular biology at Illumina. "Exciting insights into development, aging, and cancer should come quickly from understanding global patterns of DNA methylation."

The ability to rapidly read large amounts of epigenetic information is more important than the results from any one set of experiments that collect epigenetic data.

This report provides yet another illustration of how advances in instrumentation for biological systems are accelerating the rate of advance of biological science and technology.

To examine global DNA methylation patterns in human embryonic stem cells, the researchers analyzed 14 human embryonic stem cell lines from diverse ethnic origins, derived in several different labs, and maintained for various times in culture. They tested over 1500 potential methylation sites in the DNA of these cells and in other cell types and found that the embryonic stem cells shared essentially identical methylation patterns in a large number of gene regions. Furthermore, these methylation patterns were distinct from those in adult stem cells, differentiated cells, and cancer cells.

"Our results suggest that therapeutic cloning of patient-specific human embryonic stem cells will be an enormous challenge, as nuclei from adult cells will have to be epigenetically reprogrammed to reflect the specific DNA methylation signature of normal human embryonic stem cells," explains Dr. Jeanne Loring, co-director of the stem cell center at BIMR. "This reinforces the need for basic research directed at understanding the fundamental biology of human embryonic stem cells before therapeutic uses can be considered."

Some day techniques to change methylation patterns on the genome will be found. Those techniques will make it much easier to change cells into any desired cell type for therapeutic purposes. The ability to rapidly read methylation patterns will make it easier to test techniques tin the development of ways to change methylation patterns. So advances in reading methylation patterns will lead to advances for growing replacement organs and for creating stem cell therapies.

Another point: The increase in ability to read methylation patterns sounds like it was of orders of magnitude. Some people argue that anti-aging therapies are a distant prospect because even at Moore's Law (which is a doubling time for computer power of about 18 to 24 months) rates of advance it will take a long time before biotechnology cna reverse full body aging. But the advance reported above for reading methylation patterns sounds like it was much faster than the rate of Moore's Law. But biotechnology can advance more rapidly than computer technology did because biotechnology is in the process of harnessing techniques first developed for the computer industry over a period of decades.

Think of it this way: The move to put biochemical tests and sensors on chips amounts to jumping biotechnology over onto computer semiconductor technology. But that semiconductor technology took decades to develop and now biotechnology is starting to get moved over onto semiconductor devices. This allows biotech to capture in a relatively short period of time the gains of decades of semiconductor technology. So I'm not surprised to read about sudden orders of magnitude increases in the ability to do biological experiments using silicon chips.

Share |      Randall Parker, 2006 September 25 11:46 PM  Biotech Advance Rates

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