Dual-layer epigenetic gene regulation - Biological metadata points to Intelligent Design

Information layers around information layers work like a data container


Excerpt: "How can defective gene activity leading to cancer be avoided? Researchers at the University of Zurich have now identified a mechanism by which cells pass on the regulation of genetic information through epigenetic modifications. These insights open the door to new approaches for future cancer treatments.

...Methylation marks on DNA act as molecular switches that regulate gene activity in order to coordinate the cell's specialization within the organism. How this DNA methylation is faithfully regulated, and how it can become defective, has not yet been fully resolved. However, the consequences are well known: In many cancer types, the methylation is deposited in the wrong place. This leads to genes being read incorrectly.

Dual-layer epigenetic gene regulation

Scientists at the University of Zurich have now found new processes that regulate DNA methylation. Tuncay Baubec, professor at the Department of Molecular Mechanisms of Disease at the University of Zurich, and his team have shown that one particular protein plays an important part in this process: The DNA methyltransferase 3A (DNMT3A) enzyme is responsible for positioning the methylation to the right place on the DNA. "DNMT3A places itself preferably in close vicinity to genes that play an important role for development and makes sure that the DNA methylation around these genes is maintained," explains Massimiliano Manzo, lead author of the study. "The DNA methylation around these genes works like a container that ensures that H3K27me3, another epigenetic modification, which normally regulates these genes, is positioned correctly." This means that these essential genes are regulated by two epigenetic layers.
Increasing understanding of how cancer develops

The study's findings provide important basic insights for cancer research. DNMT3A is among the most frequently mutated genes in an aggressive type of leukemia, and it plays a significant role in how this disease develops. "Our findings point toward a previously unknown function of the DNMT3A protein in the interaction of these two epigenetic modifications that are normally not directly linked. We hope that these new insights will allow us to increase our understanding of the molecular mechanisms that result in cancer and to more effectively treat this aggressive type of leukemia," explains Professor Baubec."

My comment: Using containers in maintaining the integrity of biological information requires perfect software design. The DNA seems to be controlled by incredible mechanisms that refute Darwinian claims about random mutations and selection. Cellular data containers are comparable with human designed software and programming solutions. Cellular metadata points to Intelligent Design and Creation. Don't get lost.


Scientists need a human reference genome - Accurate DNA repair now possible

Lifestyle induced inheritable DNA mutations can be repaired on the atomic level

Excerpt: "Scientists at Harvard University and the Broad Institute of MIT and Harvard have developed a new class of genome editing tool. This new “base editor” can directly repair the type of single-letter changes in the human genome that account for approximately half of human disease-associated point mutations. These mutations are associated with disorders ranging from genetic blindness to sickle-cell anemia to metabolic disorders to cystic fibrosis.

The research team, led by David Liu, professor of chemistry and chemical biology at Harvard University, core institute member at the Broad Institute, and a Howard Hughes Medical Institute (HHMI) investigator, developed a molecular machine that can converts the DNA base pair A•T to G•C, without cutting the double helix, with high efficiency and virtually no undesired products. The development is an important addition to the growing suite of genome editing tools.

The new system is described in a paper published today in Nature. In addition to Liu, the study was led by Nicole Gaudelli, a postdoctoral fellow in Liu’s lab; Alexis Komor, a former postdoctoral fellow in Liu’s lab who is now an assistant professor at UCSD; graduate student Holly Rees; former graduate students Michael Packer and Ahmed Badran, and former postdoctoral fellow David Bryson.

The new system, dubbed Adenine Base Editor, or ABE, can be programmed to target a specific base pair in a genome using a guide RNA and a modified form of CRISPR-Cas9. It works by rearranging the atoms in a target adenine (A) — one of the four bases that make up DNA — to instead resemble guanine (G), and then tricking cells into fixing the other DNA strand to complete the base pair conversion, making the change permanent. As a result, what used to be an A•T base pair becomes a G•C base pair.

Not only is the system very efficient compared with other genome editing techniques for correcting point mutations, but there are virtually no detectable byproducts such as random insertions, deletions, translocations, or other base-to-base conversions.
Making this specific change is important because approximately half of the 32,000 disease-associated point mutations already identified by researchers are a change from G•C to A•T.

“We developed a new base editor — a molecular machine — that in a programmable, irreversible, efficient, and clean manner can correct these mutations in the genome of living cells,” said Liu, who is also the Richard Merkin Professor and Director of the Merkin Institute of Transformative Technologies in Healthcare at the Broad. “When targeted to certain sites in human genomic DNA, this conversion reverses the mutation that is associated with a particular disease.”
ABE joins other base-editing systems pioneered in Liu’s lab, such as BE3 and its improved variant, BE4. Using these base editors, researchers can now correct all the so-called “transition” mutations — C to T, T to C, A to G, or G to A — that together account for almost two-thirds of all disease-causing point mutations, including many that cause serious illnesses for which there are no current treatments. Additional research is needed, Liu notes, to enable ABE to target as much of the genome as possible, as Liu and his students previously achieved through engineering variants of BE3."

My comment: The most common form of point mutations in the human DNA is CG > TA due to proclivity of methylated cytosine turning to thymine in circumstances where the DNA is exposed to oxidative stress, viral attacks or other disruptive contributors. Point mutations result in faulty gene sequences that are always critical and often harmful. They are the most common reason for disease-causing genetic mutations (total number 208,368 in October 2017. Annual growth was ~20,000) in the human DNA.

Because mutations are not resulting in evolution, but genetic degradation only, scientists need this kind of new technologies for being able to repair the human DNA and to restrain devolution from happening. However, scientists need a proper human reference genome. Will people then realize that the DNA genes are not determining human traits like height, intelligence, skin color etc.? And will they also realize that the theory of Evolution is a major lie?


60,000 generations of bacteria - But evolution has not been observed

Lenski's long term experiments with bacteria contradict with evolutionary expectations


Excerpt: "You may have heard of the famous Lenski experiment. Dr. Richard E. Lenski is an evolutionary biologist who began a long-term experiment on February 24, 1988 that continues today. It looks for genetic changes in 12 initially identical populations of Escherichia coli bacteria that have been adapting to conditions in their flasks for over 60,000 generations. I have simplified a report by Scott Whynot, who studied 26 peer-reviewed scientific articles authored by Dr. Lenski (with others) published between 1991 and 2012. These papers represent the major genetic findings from 21 years of the experiment.

1. There was an insertion mutation that inhibited transcription of DNA involved in cell wall synthesis.

2. There was an insertion mutation in a regulatory region that encodes two proteins involved with cell wall synthesis. This may have led to larger cells.

3. A mutation in a gene led to a defect in DNA repair.

4. An insertion mutation may have knocked out a gene involved in programmed cell death and response to stress.

5. There was another mutation in a gene involved in response to stress, disrupting its function.

6. There was a mutation in the gene that encodes an enzyme that loosens DNA coils, leading to an increase in DNA supercoiling.

7. There was an insertion mutation in a gene that represses the production of nicotinamide adenine dinucleotide (NAD), a molecule that participates in many metabolic reactions, some affecting longevity. This might allow more NAD production.

8. The researchers noted an insertion mutation that they think inactivated a gene, resulting in greater glucose uptake. Glucose is a limited energy source in the experiment.

9. Deletion mutations caused the loss of the ability to catabolize D-ribose, an energy source that is not available in the experiment.

10. There was a mutation in a gene regulating transport of the sugar maltose, an energy source that is not present in the experiment.

11. After about 30,000 generations, the E. coli in one of the twelve isolated populations began to utilize an energy source, citrate, that they normally could not use in the presence of oxygen. E. coli already have the ability to transport and metabolize citrate where there is no oxygen, but they do not produce an appropriate transport protein for an environment with oxygen. In E. coli DNA, the gene for the citrate transporter that works without oxygen is directly upstream from genes for proteins with promoters that are active in the presence of oxygen. A replication of the region happened to put the transporter gene next to one of these promoters, so it could now be expressed in the presence of oxygen.
Except for number 11, the changes found in over 60,000 generations of bacteria were due to the disruption, degradation, or loss of genetic information. The ability to use citrate in the presence of oxygen, trumpeted by evolutionists as a big deal, was the result of previously existing information being rearranged, not the origin of new information. Mutations that result in a gain of novel information have not been observed."

My comment: 60,000 generations of bacteria show us the true nature of how adaptation of organisms occur and what it result in. Alterations in epigenetic layers lead to harmful sequence errors at the DNA level. Switching between different traits has its cost; an inevitable genetic degradation. This same phenomenon is a scientific fact within all kind of organisms in nature. Mutations are not random changes. Organisms have several mechanisms by which they are able to make use of genes. Non coding RNA molecules monitor the circumstances of surrounding environment and they transmit the information to the cell that is able to use the DNA as a library for producing necessary proteins needed in survival. The theory of evolution is a major lie, because:
- Increase of information leading to growth of structural or functional complexity has never been observed.
- Switching between diferent traits has a heavy cost: GENE LOSS.
- All changes in bacteria were due to existing biological information or rearrangement of it. Alterations occurred due to nutrition dependent reasons.
- Bacteria stay bacteria after 60,000 generations. 
- The obvious loss of genetic material has happened very fast.


Worms learn to smell danger - more than a reaction

Olfactory experience primes the heat shock transcription factor HSF-1 to enhance the expression of molecular chaperones in C. elegans


Excerpt: "Worms can learn. And the ways they learn and respond to danger could lead scientists to new treatments for people with neurodegenerative diseases.

University of Iowa researchers researchers studied how roundworms—some of the most abundant animals on Earth—react to stressful situations by exposing them to the scent of a lethal bacterium. One group of roundworms exposed to the smell primed a defense mechanism that, when activated by stress, protected the worms' cells and increased the cells' survival. The group that wasn't exposed to the odor didn't prime its defense systems. When both groups were put in physical contact with the deadly bacterium, the roundworms that were exposed to the smell activated their cellular defenses more quickly, and more survived.

The finding could usher in a new, non-pharmaceutical approach to treating neurodegenerative diseases such as Alzheimer's and Huntington's. These diseases occur when nerve cells in the brain or peripheral nervous system become damaged, lose function over time and ultimately die. Although treatments may help relieve some of the physical or mental symptoms associated with neurodegenerative diseases, there is no cure or way to slow the progression of these diseases.

The research also could help with disorders associated with aging, such as dementia, which involve the accumulation of protein damage in cells that the human central nervous system does not address, for reasons largely unknown.
"Theoretically, it should be possible to treat these types of diseases if we can figure out how to stimulate that defense mechanism in people and have it activated more consistently to fix damaged cells," says Veena Prahlad, assistant professor of biology at the UI and corresponding author on the paper, published Oct. 17 in Science Signaling. "We'd need to find the same sensory triggers in humans as we have demonstrated...in worms."

The researchers zeroed in on a defense mechanism common to all plants and animals known as the heat shock response.

This mechanism—activated by changes in temperature, salinity, and other stressors—triggers the production of a class of proteins called molecular chaperones, which seek out and repair or get rid of damaged proteins that have become toxic to the cell. The goal is to prevent an overload of damaged proteins in the cell, which would kill it.

In humans, as in the roundworms studied by Prahlad, a key protein involved in synthesizing molecular chaperones is called the heat shock transcription factor, or HSF1. Researchers know that HSF1 plays a role in guarding against protein damage in neurons that can lead to neurodegenerative diseases. But they thought it was activated only as a response to an overload of damaged proteins in cells. But Prahlad, who has studied HSF1 since she was a postdoctoral researcher, hypothesized it may be more than a reactive element. Maybe, she thought, HSF1 could be put on standby, and thus, could be activated more quickly when a threat occurs.

A big test of her idea came when she and UI graduate student and first author Felicia Ooi exposed one group of worms to the odor of the deadly bacterium PA14 while another group was given the odor of a different, benign bacterium. The group exposed to the PA14 odor activated twice the number of molecular chaperones than the group given the benign odor. Moreover, the worms exposed to the PA14 odor had a 17 percent higher survival rate after 18 hours than the worms given the odor of the benign bacterium.

Prahlad says she thinks the worms exposed to the PA14 odor "learned" the smell—and the threat that it presents—and stored that memory.

"We show in this paper that (the HSF1 response) is not a reaction," says Prahlad, who also holds an appointment in the UI's Aging Mind and Brain Initiative. "The animal turns it on in anticipation, and it does that by learning about the threat in its environment." "

My comment: Here we have a wonderful example of mechanism that refutes darwinian fairytales of mutations and selection. The fact that these smallest multicellular organisms are able to learn in such a sophisticated way points to incredible design and creation. Roundworms are able to set their defense mechanism at standby mode so that they can rapidly switch it on after sensing the danger with their olfactory receptors. Enhancing the expression of molecular chaperones, proteins that assist produced proteins to fold or unfold correctly, is an epigenetic mechanism. It's affected by miRNA regulation, DNA methylation and histone epigenetics. The link between olfactory receptors, gene expression and learning is a very interesting topic. It tells us about designed mechanisms that help and prepare organisms to survive. These mechanisms have nothing to do with random mutations and selection. The theory of evolution is a hollow fairytale. Don't get lost.


These fine-tuned protein complexes don't tolerate mutations

Cohesin and Mediator protein complexes regulate cell type specific DNA loop structures to control gene expression


Excerpt: "Each cell type, such as skin cells, nerve cells, or embryonic stem cells, has its own gene expression program to maintain its cell state. For gene activation, transcription factors and gene expression machinery (RNA polymerase), bound to two different parts of the DNA called the promoter and the enhancer, must come in contact. This contact, which is facilitated and maintained by protein complexes called Mediator and Cohesin, forms a set of DNA loops that is specific to each cell type.

Problems with this DNA loop structure can interfere with the activation of cell-type-specific genes, which can cause the cell to lose its normal state. Indeed, mutations in Mediator and Cohesin, the protein complexes that contribute to DNA loop formation, at cell-type-specific genes, can cause various developmental syndromes and diseases, including Opitz-Kaveggia syndrome, Lujan syndrome and Cornelia de Lange syndrome.

According to the Young lab’s paper, published online in Nature this week, a DNA loop formed at the beginning of cell-type-specific genes enables activation of these genes. Each cell type, such as skin cells, nerve cells, or embryonic stem cells, has its own gene expression program to maintain its cell state. For gene activation, regulatory factors and gene expression machinery, bound to two different parts of the DNA called the promoter and the enhancer, must come in contact. This contact, which is facilitated and maintained by protein complexes called Mediator and Cohesin, forms a set of DNA loops that is specific to each cell type.

“That’s such a surprise,” says Young, whose lab is deciphering the overall cellular circuitry required to regulate gene expression and cell state. “We thought that a loop of DNA probably formed at the beginning of some genes—it’s an old model—but we didn’t expect that loops are formed by these complexes at active cell-type-specific genes.”
Problems with this DNA loop structure can interfere with the activation of cell-type-specific genes, which can cause the cell to lose its normal state. Indeed, mutations in Mediator and Cohesin, the protein complexes that contribute to DNA loop formation, at cell-type-specific genes, can cause various developmental syndromes and diseases."


Excerpt: "But cohesin really only affects looping that brings genes on the same chromosome into contact. A second, still-undefined mechanism seems to bring genes from different chromosomes together, the team notes. The changing landscape of loops helps cells quickly change which genes are active."

My comment: The cell uses these protein complexes for bringing genes into contact so that gene expression is perfectly controlled. The 3D landscape is efficiently changed along the needs of adaptation or cellular differentiation program. There are several epigenetic factors affecting this 3D looping: The DNA methylation, histone markings and non coding RNA molecules. Mutations in these fine-tuned protein complexes are associated with various developmental syndromes and diseases.

These mechanisms show us again that the DNA is not controlling cellular processes. Instead, the cell uses DNA genes as it needs them for achieving its goals. These sophisticated mechanisms point to Intelligent Design and Creation.