Genetic guides to epigenetics

Genetic guides to epigenetics

Dirk Schübeler and his group at the Friedrich Miescher Institute for Biomedical Research (FMI) identify determinants that set epigenetic marks along the genome. The new study, published in Nature, shows that genetic activity and DNA sequence play a greater role in the regulation of epigenetic marking than previously thought. This questions the popular idea that gene expression can be influenced by external factors via epigenetic marking.

A popular premise of epigenetics is that our experiences can have a lasting influence on the activity of our genes, without altering the DNA sequence. This widely discussed concept proposes that we have the potential to control the epigenetic marking of our genes through our behavior. The appeal of this notion lies in its simplicity: marks placed on our DNA as a result of external factors determine which genes are switched on or off. According to this concept, hunger or stress, a happy childhood, heavy smoking or a healthy diet can influence how genes are regulated. However, convincing evidence for this popular idea is largely lacking.

Researchers at the FMI in Basel have now investigated the mechanisms that underlie the epigenetic marking of the genome. Three enzymes, known as DNA methyltransferases (DNMTs), can tag DNA with methyl groups: in this process, DNMT3A and DNMT3B create new , while DNMT1 ensures that the pattern established is propagated through each cell division.

The team of epigeneticists led by FMI Group Leader and University of Basel Professor Dirk Schübeler, demonstrated how these methylation are established. Lead author Tuncay Baubec comments: "Our studies indicate that the placement of follows defined rules. Certain patterns in the DNA sequence together with influence where the DNMTs can bind in the genome. This in turn explains the methylation patterns that arise. In this case, one can argue that can determine for themselves whether they become methylated or not."

And what about the great potential of epigenetics? Schübeler explains: "The fact that methylation patterns are largely genetically determined does not surprise us. We're glad that we now have a better understanding of the interplay between DNA sequence and methylation. This allows us to recognize where these modifications actually play a role. In addition, methylation patterns are very valuable. For example, in identifying different cell conditions. They are excellent tools for distinguishing different stages of disease, or for monitoring the effectiveness of treatment. But it's time to forget the simple notion that these markings are independent of the underlying DNA sequence."


Explore further

Deciphering the cellular reading system of DNA methylation

More information: "Genomic profiling of DNA methyltransferases reveals a role for DNMT3B in genic methylation." Nature. 2015 Jan.; DOI: 10.1038/nature14176

"Function and information content of DNA methylation." Nature 517, 321–326 (15 January 2015) DOI: 10.1038/nature14192

Journal information: Nature

Citation: Genetic guides to epigenetics (2015, February 10) retrieved 25 August 2019 from https://medicalxpress.com/news/2015-02-genetic-epigenetics.html
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Feb 10, 2015
Thanks to the research, researchers and institutions for the paradigm shift:
But it's time to forget the simple notion that these markings are independent of the underlying DNA sequence. - Schübeler


"A popular premise of epigenetics is that [DNA repair] (replaces "our experiences" in the original quote) can have a lasting influence on the activity of our genes, without altering the DNA sequence. This widely discussed concept proposes that we have the potential to control the epigenetic marking of our genes through our [repair - not behavior]. The appeal of this notion lies in its simplicity: marks placed on our DNA as a result of external factors determine which genes are switched on or off. According to this concept, hunger or stress, a happy childhood, heavy smoking, a healthy diet or [DNA repair] can influence how genes are regulated. However, convincing evidence for this popular idea is largely lacking.

Not any more

All the best to all those involved.

JVK
Feb 10, 2015
Function and information content of DNA methylation http://dx.doi.org...ure14192
Excerpt: "Genomic maps of DNA methylation have revealed unexpected dynamics at gene regulatory regions, including active demethylation by TET proteins at binding sites for transcription factors."

Genomic profiling of DNA methyltransferases reveals a role for DNMT3B in genic methylation http://dx.doi.org...ure14176
Excerpt: Together these findings reveal how sequence and chromatin cues guide de novo methyltransferase activity to ensure methylome integrity.

A symbiotic liaison between the genetic and epigenetic code http://journal.fr...113/full
Excerpt: "...the model is further extendable to virtually all traceable molecular traits."

Nutrient-dependent/pheromone-controlled adaptive evolution: a model.
http://www.ncbi.n...24693353

JVK
Feb 10, 2015
Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems
http://figshare.c...s/994281
Excerpt: "This atoms to ecosystems model of ecological adaptations links nutrient-dependent epigenetic effects on base pairs and amino acid substitutions to pheromone-controlled changes in the microRNA / messenger RNA balance and chromosomal rearrangements."

From Fertilization to Adult Sexual Behavior http://www.hawaii...ion.html

Excerpt: Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation in at least two species..."

The conserved molecular mechanisms link cell type differentiation in all cells of all individuals of all species from microbes to man. They link physics, chemistry, and communication.

JVK
Feb 10, 2015
Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems
http://figshare.c...s/994281

"...vitamin C appears to stimulate histone demethylases, which appear to alter the de novo creation of functional olfactory receptor genes (Adipietro, Mainland, & Matsunami, 2012; Blaschke et al., 2013; Jazin & Cahill, 2010; Lyons et al., 2013; Tan, Zong, & Xie, 2013)."

"The molecular mechanisms that enable this nutrient-dependent epigenetic stimulation appear to be conserved across phyla as diverse as amoeba and mammals (Hashimoto et al., 2013). Experimental evidence from studies of studies of amino acid substitutions and cell type differentiation (J. V. Kohl, 2013) suggests that a cascade of changes in protein structure and function may begin with a single vitamin-dependent base pair change (Blaschke, et al., 2013)."


Feb 11, 2015
What sort of scientific reporting is this? Its flat out misrepresenting the evidence.

From the very start it puts up a straw man: "The new study, published in Nature, shows that genetic activity and DNA sequence play a greater role in the regulation of epigenetic marking than previously thought."

Where is this previous thought from? Nowhere in epigenetics research have they assumed how much or how little DNA sequence has to do with it.

"This questions the popular idea that gene expression can be influenced by external factors via epigenetic marking."

This is not an idea, its demonstrated FACT and this study does not question that fact at all. All it does is show that the DNA methylation PATTERN depends on the DNA sequence. It does not mean that the environment cannot cause the methylation on said genes or sequence and thus change expression.

This is an incredibly bad and biased scientific article.


JVK
Feb 11, 2015
Thanks Vince Vain.
Note the comment from russell_russell
Thanks to the research, researchers and institutions for the paradigm shift


Participants in phys.org discussion know the paradigm shift started with our section on molecular epigenetics in our 1996 Hormones and Behavior review. From Fertilization to Adult Sexual Behavior http://www.hawaii...ion.html

It is now obvious to all serious scientists that the epigenetic landscape is linked to the physical landscape of DNA via nutrient-dependent RNA-mediated events and fixation of amino acid substitutions that differentiate all cell types of all individuals of all species via the biophysically constrained chemistry of protein folding.

We have reached the point where everyone must now claim: WE KNEW THAT ALL ALONG. The alternative is to admit, we knew nothing about biologically-based cause and effect in any species, so we attributed changes to evolution.

Feb 11, 2015
"...vitamin C appears to stimulate histone demethylases, which appear to alter the de novo creation of functional olfactory receptor genes (Adipietro, Mainland, & Matsunami, 2012; Blaschke et al., 2013; Jazin & Cahill, 2010; Lyons et al., 2013; Tan, Zong, & Xie, 2013)."


Where in Blaschke et al. do they discuss creation of new receptor genes? That paper's about methylation, which isn't quite a substitution. A methylated C is still a C. Histone demethylases are just another form of expression control. They have nothing to do with sequence changes. The only paper out of those that concerns changes in the genes themselves is the Adipietro one, which is chock full of evolutionary genomics, which you should be dousing in holy water for even mentioning the word "evolution".

JVK
Feb 12, 2015
Many serious scientists have been taught to use the term "evolution" for anything they cannot explain via links from physics and chemistry to molecular biology. Page limits prevent explanations in most published works, and their limited attention spans prevent science idiots from reading detailed accounts of the required links.

Even Dobzhansky (1973) used the term evolution in "Nothing in Biology Makes Any Sense Except in the Light of Evolution" where he also noted that: "...the so-called alpha chains of hemoglobin have identical sequences of amino acids in man and the chimpanzee, but they differ in a single amino acid (out of 141) in the gorilla." However, if he were not still dead, he would be using the terms 'ecological variation' and 'ecological adaptation' since serious scientists know how the epigenetic landscape is linked to the physical landscape of DNA in the organized genomes of species from microbes to man -- and it's not by mutations and evolution.

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