Epigenetics

[Phronesis]

It is about time people find out that your genetic make-up does not entirely determine who they are. Mutations happen and they irreversibly alter a person's make-up.

Enter epigenetics and the epigenetic machinery:
While the genetic code is being copied during cell division, another set of machines copy the epigenetic code. How you may ask? Part of the answer lies with the ability of epigenetically related enzymes and their ability to methylate and demethylate cytosine (one of the DNA bases). The methylation status of cytosine acts as a switch for genes. Hypermethylated regions act as suppressors of gene activity.
The difference between genetics and epigenetics is that the epigenetic status of a stretch of DNA bases is reversible, while mutations are permanent if not fixed during replication.
Article:
Rethinking The Genetic Theory Of Inheritance: Heritability May Not Be Limited To DNA

ScienceDaily (Jan. 20, 2009) — Scientists at the Centre for Addiction and Mental Health (CAMH) have detected evidence that DNA may not be the only carrier of heritable information; a secondary molecular mechanism called epigenetics may also account for some inherited traits and diseases. These findings challenge the fundamental principles of genetics and inheritance, and potentially provide a new insight into the primary causes of human diseases.

Your mother's eyes, your father's height, your predisposition to disease-- these are traits inherited from your parents. Traditionally, 'heritability' is estimated by comparing monozygotic (genetically identical) twins to dizygotic (genetically different) twins. A trait or disease is called heritable if monozygotic twins are more similar to each other than dizygotic twins. In molecular terms, heritability has traditionally been attributed to variations in the DNA sequence.

CAMH's Dr. Art Petronis, head of the Krembil Family Epigenetics Laboratory, and his team conducted a comprehensive epigenetic analysis of 100 sets of monozygotic and dizygotic twins in the first study of its kind. Said Dr. Petronis, "We investigated molecules that attach to DNA and regulate various gene activities. These DNA modifications are called epigenetic factors."

The CAMH study showed that epigenetic factors – acting independently from DNA – were more similar in monozygotic twins than dizygotic twins. This finding suggests that there is a secondary molecular mechanism of heredity. The epigenetic heritability may help explain currently unclear issues in human disease, such as the presence of a disease in only one monozygotic twin, the different susceptibility of males (e.g. to autism) and females (e.g. to lupus), significant fluctuations in the course of a disease (e.g. bipolar disorder, inflammatory bowel disease, multiple sclerosis), among numerous others.

"Traditionally, it has been assumed that only the DNA sequence can account for the capability of normal traits and diseases to be inherited," says Dr. Petronis. "Over the last several decades, there has been an enormous effort to identify specific DNA sequence changes predisposing people to psychiatric, neurodegenerative, malignant, metabolic, and autoimmune diseases, but with only moderate success. Our findings represent a new way to look for the molecular cause of disease, and eventually may lead to improved diagnostics and treatment."

This is crucial especially for women as their actions during pregnancy will have a huge impact on how a child develops. A person with a perfect DNA make-up can end-up with defects as a result of the actions of the mother. This has been known for a while obviously, but it is now clear it is not determined by genetics, but epigenetics and humans are in full control of their destiny and their ability to steer development.

Also important is that you also have an effect on how you develop. Eat too much or exercise too little and become obese and it might negatively affect the methylation status of tumour-suppressor genes, leading to an increased
susceptibility to develop cancer.

Scientists are slowly starting to crack yet another code of life... the epigenetic code.

 

[mercurial]

You may want to have a look at Scripps institute. They found that certain RNA can replicate themselves.

http://www.eurekalert.org/pub_releases/2009-01/sri-ssd010909.php

 

[Phronesis]

You may want to have a look at Scripps institute. They found that certain RNA can replicate themselves.

http://www.eurekalert.org/pub_releases/2009-01/sri-ssd010909.php

How is this relevant to epigenetics? Besides, that discovery was posted here first . About the same validity to abiogenesis as the Ghadiri protein...

 

[mercurial]

How is this relevant to epigenetics? Besides, that discovery was posted here first . About the same validity to abiogenesis as the Ghadiri protein...

Does this not deal with mutation and DNA replication?

 

[Phronesis]

No. And this thread discusses epigentics.

 

[mercurial]

Rubbish. You specifically spoke about mutation and DNA replication in your OP. Oh well, I should have known better than post in a RAS thread.

 

[Phronesis]

Did you read the whole OP with comprehension? Or did you just see the words "replication" and "mutation"? Self-replicating RNA in the article you cited is associated with abiogenesis (off topic), mutations are associated with genetics (related but not the same as epigenetics). This thread focuses on epigenetics. Methylation and demethylation patterns of DNA and how it affects development. Mutations and replication were mentioned to show how they are related, but also to highlight the differences so that this hread can focus on epigenetic and NOT genetics or abiogenesis .

 

[Phronesis]

A simple example is the development process.
Large DNA Stretches, Not Single Genes, Shut Off As Cells Mature

ScienceDaily (Jan. 18, 2009) — Experiments at Johns Hopkins have found that the gradual maturing of embryonic cells into cells as varied as brain, liver and immune system cells is apparently due to the shut off of several genes at once rather than in individual smatterings as previous studies have implied.

Working with mouse brain and liver cells, as well as embryonic stem cells, Johns Hopkins University School of Medicine professor Andrew Feinberg, M.D., M.P.H., led an investigation of a kind of epigenetic modification to histones, the molecular "spools" that DNA winds around in the cell nucleus. This modification is a variety of the so-called epigenetic changes that alter the function of cells without directly altering the nuclear DNA in the cells.

Histones are part of the epigenetic machinery. Histone modification as a result of environmental cues plays crucial roles in the development of various diseases, including cancer.

Other scientists had previously found that histone modifications appear to silence individual genes in the DNA that coils around affected histones. But when Feinberg and his team compared the activity of thousands of genes in the liver and brain cells, they found that a particular modification — in which two methyl groups clip onto histones — seemed to silence long stretches of DNA containing many genes at once.

Since the silenced stretches varied greatly between the different types of cells, Feinberg, postdoctoral fellow Bo Wen, and their colleagues wondered whether these sections — called large organized chromatin K9 modifications, or LOCKS — might be responsible for the transition from the "blank slate" quality of embryonic cells to the specialized functions that mature cells take on. To find out, he and his team looked for LOCKs in mouse embryonic stem cells. Unlike mature, adult liver and brain cells, in which about 40 percent of the genome was silenced by LOCKs, the embryonic stem cells had no LOCKs.

Next, the researchers compared the regions of DNA affected by LOCKs between mouse liver and brain cells and their corresponding human cells. The same cell types in both organisms had remarkably similar regions of DNA silenced by LOCKs, suggesting that the same genes necessary to control cell function are affected in mice and people.

"These results suggest that LOCKs appear gradually during development, refining cells' functions as they differentiate into particular cell types," Wen says. "Our experiments suggest that the whole forest of genes is changing, but people have been looking at the individual trees."

Because epigenetic changes also are known to play a role in abnormal cell growth, the researchers suspected that LOCKs were involved in the development of cancer. When they looked for genes in several common cancer cell lines often used in research, they indeed found significantly fewer LOCKs than in normal liver and brain cells.

"In cancer, some of these LOCKs may become unlocked," says Feinberg. "Sections of DNA that were silenced in a cell type might become active, giving cancer cells characteristics of other cell types that they're not supposed to have."

Feinberg says this "unlocking" might cause cancer cells to revert to a more immature developmental state, explaining some of their unusual behavior, such as extreme proliferation or migration to different areas of the body.

The findings will publish in Nature Genetics online on Jan. 18. Other researchers who participated in this study include Hao Wu and Rafael Irizarry, both of the Johns Hopkins University Bloomberg School of Public Health, and Yoichi Shinkai of Kyoto University.

Your actions predispose (or protects) you from disease and the mechanism is not related to genetics, but epigenetics.

One thing that is different in epigenetics is that it is reprogrammable. Unlike a mutation that is permanent and can cause damage, epigenetic changes are reversible. Like a computer that is able to write and delete on a hard drive, so does the epigenetic machinery act to add or remove methyl grouprs to cytosine bases.

This knowledge was used to fuel the discovery of last year’s best scientific breakthrough.
Reprogramming cells to possibly provide a cure for vexing conditions such as Alzheimers and Parkinsons and possibly even spinal cord injuries

 

[stoke]

Thank you Phronesis, interesting.

 

[Phronesis]

Thank you Phronesis, interesting.

Pleasure .

New Class Of Non-protein Coding Genes In Mammals With Key Functions Uncovered

ScienceDaily (Feb. 1, 2009) — A research team at the Broad Institute of Harvard and MIT and Beth Israel Deaconess Medical Center has uncovered a vast new class of previously unrecognized mammalian genes that do not encode proteins, but instead function as long RNA molecules.

Some were even of the opinion it was leftovers of messy, badly designed evolutionary processes. Not so.

Their findings, published in the February 1st advance online issue of the journal Nature, demonstrate that this novel class of "large intervening non-coding RNAs" or "lincRNAs" plays critical roles in both health and disease, including cancer, immune signaling and stem cell biology.

"We've known that the human genome still has many tricks up its sleeve," said Eric Lander, founding director of the Broad Institute and co-senior author of the Nature paper. "But, it is astounding to realize that there is a huge class of RNA-based genes that we have almost entirely missed until now.

The rabbit hole gets deeper. And now the link to epigenomics.

"The epigenomic marks revealed where these genes were hiding," said Mitch Guttman, a MIT graduate student working at the Broad Institute. "Analysis of their sequence then revealed that the genes are highly conserved in mammalian genomes, which strongly suggested that these genes play critical biological functions."

By correlating the expression patterns of lincRNAs in various cell types with the expression patterns of known critical protein-coding genes in those same cells, the scientists observed that lincRNAs likely play critical roles in helping to regulate a variety of different cellular processes, including cell proliferation, immune surveillance, maintenance of embryonic stem cell pluripotency, neuronal and muscle development, and gametogenesis. Further experimental evidence from several of the identified lincRNAs verified these observations.

Because of the stringent experimental conditions imposed by the researchers in identifying the 1,600 lincRNAs in the Nature study, it is likely that there are many more lincRNA genes hiding in plain sight in the genome, as well as other RNA-encoding genes that are as important to genome function as their better-recognized protein-coding counterparts.

The epigenetic machinery can switch the activity of genes on and off in response to the environment. These new lincRNAs is another piece of the puzzle in cracking the epigenetic code. The next step is to uncover how this code is structured and why it functions the way it does. Who knows, perhaps we can use the design principles discovered in epigenetics to design our own optimal, structured and coded systems.

 

[Phronesis]

New nucleotide could revolutionize epigenetics

The discovery of a new nucleotide in the mouse brain opens the door to a new domain of epigenetic DNA modification

Anyone who studied a little genetics in high school has heard of adenine, thymine, guanine and cytosine – the A,T,G and C that make up the DNA code. But those are not the whole story. The rise of epigenetics in the past decade has drawn attention to a fifth nucleotide, 5-methylcytosine (5-mC), that sometimes replaces cytosine in the famous DNA double helix to regulate which genes are expressed. And now there's a sixth. In experiments to be published online Thursday by Science, researchers reveal an additional character in the mammalian DNA code, opening an entirely new front in epigenetic research.

The work, conducted in Nathaniel Heintz's Laboratory of Molecular Biology at The Rockefeller University, suggests that a new layer of complexity exists between our basic genetic blueprints and the creatures that grow out of them. "This is another mechanism for regulation of gene expression and nuclear structure that no one has had any insight into," says Heintz, who is also a Howard Hughes Medical Institute investigator. "The results are discrete and crystalline and clear; there is no uncertainty. I think this finding will electrify the field of epigenetics."

Genes alone cannot explain the vast differences in complexity among worms, mice, monkeys and humans, all of which have roughly the same amount of genetic material. Scientists have found that these differences arise in part from the dynamic regulation of gene expression rather than the genes themselves. Epigenetics, a relatively young and very hot field in biology, is the study of nongenetic factors that manage this regulation.

One key epigenetic player is DNA methylation, which targets sites where cytosine precedes guanine in the DNA code. An enzyme called DNA methyltransferase affixes a methyl group to cytosine, creating a different but stable nucleotide called 5-methylcytosine. This modification in the promoter region of a gene results in gene silencing.

Some regional DNA methylation occurs in the earliest stages of life, influencing differentiation of embryonic stem cells into the different cell types that constitute the diverse organs, tissues and systems of the body. Recent research has shown, however, that environmental factors and experiences, such as the type of care a rat pup receives from its mother, can also result in methylation patterns and corresponding behaviors that are heritable for several generations. Thousands upon thousands of scientific papers have focused on the role of 5-methylcytosine in development.

The discovery of a new nucleotide may make biologists rethink their approaches to investigating DNA methylation. Ironically, the latest addition to the DNA vocabulary was found by chance during investigations of the level of 5-methylcytosine in the very large nuclei of Purkinje cells, says Skirmantas Kriaucionis, a postdoctoral associate in the Heintz lab, who did the research. "We didn't go looking for this modification," he says. "We just found it."

Kriaucionis was working to compare the levels of 5-methylcytosine in two very different but connected neurons in the mouse brain — Purkinje cells, the largest brain cells, and granule cells, the most numerous and among the smallest. Together, these two types of cells coordinate motor function in the cerebellum. After developing a new method to separate the nuclei of individual cell types from one another, Kriaucionis was analyzing the epigenetic makeup of the cells when he came across substantial amounts of an unexpected and anomalous nucleotide, which he labeled 'x.'

It accounted for roughly 40 percent of the methylated cytosine in Purkinje cells and 10 percent in granule neurons. He then performed a series of tests on 'x,' including mass spectrometry, which determines the elemental components of molecules by breaking them down into their constituent parts, charging the particles and measuring their mass-to-charge ratio. He repeated the experiments more than 10 times and came up with the same result: x was 5-hydroxymethylcytosine, a stable nucleotide previously observed only in the simplest of life forms, bacterial viruses. A number of other tests showed that 'x' could not be a byproduct of age, DNA damage during the cell-type isolation procedure or RNA contamination. "It's stable and it's abundant in the mouse and human brain," Kriaucionis says. "It's really exciting."

What this nucleotide does is not yet clear. Initial tests suggested that it may play a role in demethylating DNA, but Kriaucionis and Heintz believe it may have a positive role in regulating gene expression as well. The reason that this nucleotide had not been seen before, the researchers say, is because of the methodologies used in most epigenetic experiments. Typically, scientists use a procedure called bisulfite sequencing to identify the sites of DNA methylation. But this test cannot distinguish between 5-hydroxymethylcytosine and 5-methylcytosine, a shortcoming that has kept the newly discovered nucleotide hidden for years, the researchers say. Its discovery may force investigators to revisit earlier work. The Human Epigenome Project, for example, is in the process of mapping all of the sites of methylation using bisulfite sequencing. "If it turns out in the future that (5-hydroxymethylcytosine and 5-methylcytosine) have different stable biological meanings, which we believe very likely, then epigenome mapping experiments will have to be repeated with the help of new tools that would distinguish the two," says Kriaucionis.

Providing further evidence for their case that 5-hydroxymethylcytosine is a serious epigenetic player, a second paper to be published in Science by an independent group at Harvard reveals the discovery of genes that produce enzymes that specifically convert 5-methylcytosine into 5-hydroxymethylcytosine. These enzymes may work in a way analogous to DNA methyltransferase, suggesting a dynamic system for regulating gene expression through 5-hydroxymethylcytosine. Kriaucionis and Heintz did not know of the other group's work, led by Anjana Rao, until earlier this month. "You look at our result, and the beautiful studies of the enzymology by Dr. Rao's group, and realize that you are at the tip of an iceberg of interesting biology and experimentation," says Heintz, a neuroscientist whose research has not focused on epigenetics in the past. "This finding of an enzyme that can convert 5-methylcytosine to 5-hydroxymethylcytosine establishes this new epigenetic mark as a central player in the field."

Kriaucionis is now mapping the sites where 5-hydroxymethylcytosine is present in the genome, and the researchers plan to genetically modify mice to under- or overexpress the newfound nucleotide in specific cell types in order to study its effects. "This is a major discovery in the field, and it is certain to be tied to neural function in a way that we can decipher," Heintz says.

Fascinating research awaits...

 

[Phronesis]

We are more than just genes....
Say hi to your epigenome and epigenetic inheritance:

Epigenetics: 100 Reasons To Change The Way We Think About Genetics

ScienceDaily (May 20, 2009) — For years, genes have been considered the one and only way biological traits could be passed down through generations of organisms.

Not anymore.
Increasingly, biologists are finding that non-genetic variation acquired during the life of an organism can sometimes be passed on to offspring—a phenomenon known as epigenetic inheritance. An article forthcoming in the July issue of The Quarterly Review of Biology lists over 100 well-documented cases of epigenetic inheritance between generations of organisms, and suggests that non-DNA inheritance happens much more often than scientists previously thought.

Biologists have suspected for years that some kind of epigenetic inheritance occurs at the cellular level. The different kinds of cells in our bodies provide an example. Skin cells and brain cells have different forms and functions, despite having exactly the same DNA. There must be mechanisms—other than DNA—that make sure skin cells stay skin cells when they divide.

Genes are like the software code of your operating system.
The epigenome works like a printer that interacts with the environment and imprints information from the environment onto your genetic software system through methylation and demethylation of cytosine (and another new one labelled X). What makes it different from normal mutations is that it is reversible.

We all dance to the tune of our little nano-intentional molecular autonomous agents.... cells.
Governed by biomolecular machines and a superbly optimal genetic code...
Science and the scientific method is only beginning to uncover the mysteries of life...
Enjoy:
[ame]http://www.youtube.com/watch?v=-yLKa_i4MCQ[/ame]

 

[Phronesis]

New Piece Found In The Puzzle Of Epigenetics: Mechanism Of Fine Regulation Of RNA Synthesis Elucidated

ScienceDaily (June 16, 2009) — A team of scientists led by Professor Dirk Eick of Helmholtz Zentrum München has identified the enzyme TFIIH kinase as an important factor in the epigenetic regulation of the cell nucleus enzyme RNA polymerase II. The findings, recently published in the journal Molecular Cell, constitute a further building block for understanding the pathomechanisms of cancer and other diseases.

For many years scientists have known that the numerous biological functions of an organism are not regulated solely by the DNA sequence of its genes: Superordinate regulatory mechanisms exist that contribute to determining the fate of genes. Although they are not anchored in the DNA, they can even be passed on to subsequent generations to a certain extent. Intensive research in recent years has shown that these mechanisms – bundled under the term epigenetics, are very multifaceted and complex.

Professor Dirk Eick and staff members of the Institute of Clinical Molecular Biology and Tumor Genetics of Helmholtz Zentrum München, together with colleagues from the University of Wisconsin-Madison, Wisconsin, USA, have now identified another piece in the puzzle of epigenetics: They showed that the enzyme TFIIH kinase is involved in epigenetic regulation.

The scientists were interested in the fine regulation of the cell nucleus enzyme RNA polymerase II. This transcribes the genetic information of the genetic substance DNA into messenger RNA - mRNA for short – which in turn is the basis for protein synthesis. At the same time RNA polymerase II is also responsible for the production of other kinds of RNA molecules, the so-called snRNA, which are not translated into proteins but take on other tasks. In prior research Eick and his colleagues had observed that a certain region of the RNA polymerase II enzyme – the carboxy-terminal domain – is involved in deciding which kinds of RNA are formed. In humans this domain consists of 52 repeats of a sequence of seven amino acids.

For RNA synthesis the determining factor is whether and how specific amino acids of this region are modified biochemically. Thus, it is absolutely essential for the synthesis of snRNA that the amino acid serine at position 7 of this repeat sequence is provided with an additional phosphate group. If this is lacking, mRNA will be produced, but not any snRNA. The reasonfor that is presumably that this phosphorylation enables the interaction with a protein complex – the so-called integrator complex – which is necessary for snRNA formation. In other words, the modification of the enzyme RNA polymerase II at defined positions regulates whether this enzyme can produce certain kinds of RNA molecules or not.

In their latest research, the scientists led by Dirk Eick showed that the enzyme TFIIH kinase is responsible for the selective phosphorylation of RNA polymerase II. “With these findings another building block has been identified that plays a key role in epigenetic regulation by means of RNA polymerase II,” Professor Eick said. “This is of great significance because knowledge of epigenetic mechanisms is necessary in order to better understand cancer and other diseases and to be able to provide more targeted treatment.”

 

[Phronesis]

Are We What Our Mothers Ate?

ScienceDaily (July 22, 2009) — Mothers' health in the days and weeks prior to becoming pregnant may determine the health of offspring much later in life, according to results of studies reported at the annual meeting of the Society for the Study of Reproduction, which takes place July 18 to 22 at the David L. Lawrence Convention Center in Pittsburgh. These studies demonstrate that maternal nutrition, protein intake and level of fat in the diet may cause epigenetic changes in the developing fetus that can have long-term health consequences.

Too Much of a Sweet Thing? Maternal Diabetes and Embryo Development

The time between ovulation and conception may be a critical one for maternal and fetal health, according to Kelle Moley, M.D., Washington University School of Medicine. In mouse studies, she found that subtle differences in maternal metabolism had long-lasting effects. Indeed, when Dr. Moley transferred embryos from a diabetic mouse into a non-diabetic mouse shortly after egg implantation, she noted neural tube defects, heart defects, limb deformities and growth defects in offspring. These findings indicate that we may need to re-direct our ideas about maternal health to the time prior to pregnancy, she says.

Take Your Vitamins Before Becoming Pregnant

Are we encouraging pregnant women to take vitamins when it may be too late to impact the health of a growing fetus? According to Kevin Sinclair, Ph.D., University of Nottingham, maternal nutrition even at the time of conception can alter fetal development. In studies with sheep and rodents, he found that offspring of mothers with vitamin B12 and folic acid deficiencies were fatter, became insulin resistant and had higher blood pressure by the time they reached middle-age, demonstrating that early molecular changes may not manifest themselves for many years.

Low Protein Diet May Lead to "Jumpy" Offspring

Low protein levels in female mice during the first few moments of conception, when the egg is still dividing, caused abnormal growth, cardiovascular disease, high blood pressure and jumpy behavior in their offspring. According to Tom Fleming, Ph.D., University of Southampton, mice born to mothers with low protein grew bigger – extracting as much nutrients as they could to compensate for poor nutrition while in the womb.

Beyond Genetics: How Dormant Memories Can Impact Later-Life Events

According to epigenetic theory, changes in the genome can happen at any time through the impact of environmental factors on the expression of genes over time. One of the most critical periods is early life when epigenetic memories are created that may impact a person's susceptibility to disease later in life, says Shuk-mei Ho, Ph.D., University of Cincinnati Medical Center. According to her research, these "memories" may remain dormant until an environmental trigger brings them to the surface, modifying risk for disease.

The scientists discussed their research during a briefing, "The Origins of Adult Disease,"on July 21 at the David L. Lawrence Convention Center, Pittsburgh.

 

[Phronesis]

A little bit of everything:
Epigenetics and nucleosomes.
Biomolecular machines and cellular memory and RNA splicing...
Preadaptations and the existence of the epigentic machinery.

Epigenetics: Evolutionarily Preserved Mechanism Governs Use Of Genes

ScienceDaily (Aug. 18, 2009) — Researchers at Uppsala University have found that the protein coding parts of a gene are packed in special nucleosomes. The same type of packaging is found in the roundworm C elegans, which is a primeval relative of humans. The mechanism can thereby be traced back a billion years in time, according to the study presented in the journal Genome Research.

Human genes are packed in nucleosomes, which contain epigenetic signals directing how the genes are to be used. The cell nucleus contains DNA, which is wound around proteins to form units called nucleosomes, not unlike pearls on a string. Genes on average contain ten protein coding units called exons. Previously there was no known correlation between nucleosomes and exons . New results show that nucleosomes are placed over exons. This means that the area containing the protein code is packed in discrete units.

These results are presented by a research team at Uppsala University, led by Professor Claes Wadelius at the Department of Genetics and Pathology and Professor Jan Komorowski at the Linnaeus Centre for Bioinformatics as well as University of Warsaw.

Epigenetics is a cellular memory which identifies a cell's identity and way to respond to the environment. Epigenetic signals control genes in a flexible manner. Each genetic package, or pearl on the string, has an epigenetic signal indicating how active it is. In the present study it was shown that there is a previously undiscovered epigenetic mark on protein coding parts of the gene.

"A gene can be read in several ways and create different proteins. We have now demonstrated that there is an epigenetic control that determines which parts of the gene that are read," says Claes Wadelius.

The study is based on extremely large amounts of data published by other scientists, but not previously analyzed in such detail.

"Our findings show the value of sophisticated bioinformatic analyses and the need to delve deeper into the gigantic amounts of data from modern biological research," says Jan Komorowski.

The scientists also show that the same type of genetic packaging exists in the tiny roundworm C elegans. Humans are related to this worm through a common ancestor that lived a billion years ago. This means that the mechanism has been evolutionarily preserved during nearly one fourth of the time the earth has existed eller one fourth of earth's existence. In humans, the genetic code has been divided into smaller parts that fit into the individual packages or pearls.

"This enables a gene to be used in several different ways. This has probably contributed to human development," concludes Professor Claes Wadelius.

 

[Phronesis]

What Drives Our Genes? Researchers Map The First Complete Human Epigenome

ScienceDaily (Oct. 15, 2009) — Although the human genome sequence faithfully lists (almost) every single DNA base of the roughly 3 billion bases that make up a human genome, it doesn't tell biologists much about how its function is regulated. Now, researchers at the Salk Institute provide the first detailed map of the human epigenome, the layer of genetic control beyond the regulation inherent in the sequence of the genes themselves.

Although the human genome sequence faithfully lists (almost) every single DNA base of the roughly 3 billion bases that make up a human genome, it doesn't tell biologists much about how its function is regulated. (Credit: iStockphoto/Andrey Prokhorov)​

"In the past we've been limited to viewing small snippets of the epigenome," says senior author Joseph Ecker, Ph.D., professor and director of the Genomic Analysis Laboratory at the Salk Institute and a member of the San Diego Epigenome Center. "Being able to study the epigenome in its entirety will lead to a better understanding of how genome function is regulated in health and disease but also how gene expression is influenced by diet and the environment."

Their study, published in the Oct. 14, 2009 advance online edition of the journal Nature, compared the epigenomes of human embryonic stem cells and differentiated connective cells from the lung called fibroblasts, revealing a highly dynamic, yet tightly controlled, landscape of chemical signposts known as methyl-groups. The head-to-head comparison brought to light a novel DNA methylation pattern unique to stem cells, which may explain how stem cells establish and maintain their pluripotent state, the researchers say.

The emergence of epigenetics has already changed the way researchers think about how disease arises and how physicians treat it. Epigenetic changes play a crucial role in the development of cancer and some drugs that directly interact with the epigenome have been approved for the treatment of lymphoma and lung cancer and are now tested against a number of other cancer types. "Unless we know how these drugs affect the entire epigenome, we don't really understand their full mechanism of action," says Ecker.

Recognizing the central role of the epigenome in many areas of biology and medicine the National Institutes of Health launched a five-year Roadmap Epigenomics Program in 2008. The San Diego Epigenome Center, headed by Bing Ren, Ph.D., Professor of Cellular and Molecular Medicine at the University of California, San Diego School of Medicine and head of the Laboratory of Gene Regulation at the Ludwig Institute for Cancer Research, is an integral part of the five-year, $190 million push to accelerate research into modifications that alter genetic behavior across the human genome.

The current study, to which Ren and additional members of the Center located at the University of Wisconsin and the Morgridge Institute for Research in Madison, Wisconsin, also contributed, is not only the first complete high-resolution map of an epigenome superimposed on the human genome, but also the first study to be published as a direct result of the Roadmap Epigenomics Program.

"This paper exemplifies the goals of the NIH Roadmap for Medical Research's Epigenomics Program," said Linda Birnbaum, Ph.D., director of the National Institute of Environmental Health Sciences, one of the NIH institutes funding this program. "The science has matured to a point that we can now map the epigenome of a cell. This paper documents the first complete mapping of the methylome, a subset of the entire epigenome, of 2 types of human cells - an embryonic stem cell and a human fibroblast line. This will help us better understand how a diseased cell differs from a normal cell, which will enhance our understanding of the pathways of various diseases."

Epigenetic signals can tinker with genetic information in at least two ways: One targets histones, the "spools" around which DNA winds and which control access to DNA. The other is DNA methylation, a chemical modification of one letter, C (cytosine), of the four letters (A, G, C, and T) that comprise our DNA. In the last couple of years, Ecker's laboratory started to zoom in on genomic methylation patterns, which are essential for normal development and are associated with a number of key cellular processes, including carcinogenesis.

Perfecting the technique in Arabidopsis thaliana, a plant whose genome is 25 times smaller than the human genome, Ryan Lister, Ph.D., a postdoctoral researcher in Ecker's lab and co-first author on the current study, developed an ultra high-throughput methodology to precisely determine whether each C in the genome is methylated or not, and layer the resulting epigenomic map upon the exact genome it regulates.

He then put the brand new technology to work to map the epigenomes of differentiated fibroblast cells and human embryonic stem cells (hESCs.) "We wanted to know how the epigenome of a differentiated cell that's programmed to perform a specific job differs from the epigenome of a pluripotent stem cell, that has the potential to turn into any other cell type," Lister says.

Just as expected, in fibroblast cells the majority of Cs followed by a G carried a methyl-group, a pattern often referred to as CG-methylation. But much to the Salk researchers' surprise, in embryonic stem cells about a quarter of all methylation events occurred in a different context.

"Non-CG methylation is not completely unheard of -- people have seen it in dribs and drabs, even in stem cells. But nobody expected that it would be so extensive," says postdoctoral researcher and co-first author Mattia Pelizzola, who along with Lister undertook the extensive task of extracting and analyzing the epigenome data from these vast sequence datasets. "The whole field had been focused on CG methylation, and non-CG methylation was often considered a technical artifact."

To confirm their finding, the authors then targeted several regions in a second hESC line, as well as in fibroblast cells that had been reprogrammed into so called induced pluripotent stem (iPS) cells. "They both had the same high level of non-CG methylation, which was lost when we forced them to differentiate," says Pelizzola.

Being able to create high resolutions maps of the human epigenome, Ecker's group will now begin to examine how it changes during normal development as well as examining a variety of disease states. "For the first time, we will be able to see the fine details of how DNA methylation changes in stem cells and other cells as they grow and develop into new cell types," he says. "We believe this knowledge will be extremely valuable for understanding diseases such as cancer and possibly even mental disorders. Right now we just don't know how the epigenome changes during the aging process or how the epigenome is impacted by our environment or diet."

This work was supported in part by grants from the Mary K. Chapman Foundation, the NIH, the California Institute for Regenerative Medicine, the Australian Research Council Centre of Excellence Program and the Morgridge Institute for Research.

Researchers who also contributed to the work include Robert H. Dowen and Joseph R. Nery in the Genomic Analysis Laboratory, Gary Hon, Leonard Lee, Zhen Ye, Que-Minh Ngo and Lee Edsall at the Ludwig Institute for Cancer Research at the University of California San Diego, Julian Tonti-Filippini and A. Harvey Millar at the ARC Center of Excellence in Plant Energy Biology in Crawley, Australia, Jessica Antosiewicz-Bourget, Ron Stewart, Victor Ruotti and James A. Thomson at the Morgridge Institute for Research and at the Genome Center of Wisconsin, both at the University of Wisconsin in Madison.

Welcome to the wonderful world of epigenetics.

 

[Phronesis]

Scientists Reveal How Induced Pluripotent Stem Cells Differ From Embryonic Stem Cells

ScienceDaily (Nov. 9, 2009) — The same genes that are chemically altered during normal cell differentiation, as well as when normal cells become cancer cells, are also changed in stem cells that scientists derive from adult cells, according to new research from Johns Hopkins and Harvard.

Methylation and epigenetic status plays a crucial role....

 

[mister]

To those just getting started I highly recommend:

The Biology of Belief: Unleashing the Power of Consciousness, Matter, & Miracles by Bruce H. Lipton Ph.D. (Hardcover - Sep 15, 2008)

Quote:

"This book is a groundbreaking work in the field of new biology, and it will forever change how you think about thinking. Through the research of Dr. Lipton and other leading-edge scientists, stunning new discoveries have been made about the interaction between your mind and body and the processes by which cells receive information. It shows that genes and DNA do not control our biology, that instead DNA is controlled by signals from outside the cell, including the energetic messages emanating from our thoughts. Using simple language, illustrations, humor, and everyday examples, he demonstrates how the new science of Epigenetics is revolutionizing our understanding of the link between mind and matter and the profound effects it has on our personal lives and the collective life of our species."

 

[Jenemesis]

Agreed
many deseases are psychosomatic
I have proof

 

[wrathex]

Mind and matter

Agreed
many deseases are psychosomatic
I have proof

Just over a decade ago, I had a nervous breakdown, along with a severe bipolar episode due to spouse having an affair.

I became very ill mentally and eventually physically.

My limbs pained and started stiffening. This took place over a period of several months.

I had a lot of bloodwork done, saw many specialists, no results, nothing detected.

My arms became lame and then my legs, my hands started curling into tight balls, I had excruciating pain.

I was in a state of inability to function normally for several weeks.

Eventually my psychiatrist conceded that I was manifesting it myself.

(I was treated with the appropriate chemicals and underwent intense cognitive therapy
- I made a quick physical recovery and I was aghast
at what I had done to myself, but I also learned a very valuable lesson and since then have a lot more respect for my conscious consciousness and the
obvious implication that mind influences matter willfully albeit subconsciousely)

This is a personal experience of thought influencing the physical world.

(evidence of quantum interaction )