2017/08/18

Intergenerational inheritance of epigenetic information

Intergenerational inheritance of epigenetic information - why we can observe changes in organisms

https://www.news-medical.net/news/20170718/Study-provides-insights-into-intergenerational-inheritance-of-epigenetic-information.aspx

Summary:
  • Epigenetic mechanisms modulated by environmental cues such as diet, disease or our lifestyle take a major role in regulating the DNA by switching genes on and off, and activating/silencing regions of the DNA.
  • Mother's epigenetic memory is essential for the development and survival of the new generation.
  • Epigenetic modifications label specific regions of the DNA to attract or keep away proteins (transcription factors) that activate genes.
  • Epigenetic marks can also change throughout our life and in response to our environment or lifestyle.
  • Inherited epigenetic information is needed to process and correctly transcribe the genetic code of the embryo.
  • Epigenetic marks transmitted from the mother are a fine-tuned mechanism to control gene activation during the complex process of early embryogenesis.
  • Disruption of epigenetic mechanisms may cause diseases such as cancer, diabetes and autoimmune disorders.
Excerpt: "We are more than the sum of our genes. Epigenetic mechanisms modulated by environmental cues such as diet, disease or our lifestyle take a major role in regulating the DNA by switching genes on and off. It has been long debated if epigenetic modifications accumulated throughout the entire life can cross the border of generations and be inherited to children or even grand children. Now researchers from the Max Planck Institute of Immunobiology and Epigenetics in Freiburg show robust evidence that not only the inherited DNA itself but also the inherited epigenetic instructions contribute in regulating gene expression in the offspring. Moreover, the new insights by the Lab of Nicola Iovino describe for the first time biological consequences of this inherited information. The study proves that mother's epigenetic memory is essential for the development and survival of the new generation.
 
In our body we find more than 250 different cell types. They all contain the exact same DNA bases in exactly the same order; however, liver or nerve cells look very different and have different skills. What makes the difference is a process called epigenetics. Epigenetic modifications label specific regions of the DNA to attract or keep away proteins that activate genes. Thus, these modifications create, step by step, the typical patterns of active and inactive DNA sequences for each cell type. Moreover, contrary to the fixed sequence of 'letters' in our DNA, epigenetic marks can also change throughout our life and in response to our environment or lifestyle. For example, smoking changes the epigenetic makeup of lung cells, eventually leading to cancer. Other influences of external stimuli like stress, disease or diet are also supposed to be stored in the epigenetic memory of cells.

It has long been thought that these epigenetic modifications never cross the border of generations. Scientists assumed that epigenetic memory accumulated throughout life is entirely cleared during the development of sperms and egg cells. Just recently a handful of studies stirred the scientific community by showing that epigenetic marks indeed can be transmitted over generations, but exactly how, and what effects these genetic modifications have in the offspring is not yet understood. "We saw indications of intergenerational inheritance of epigenetic information since the rise of the epigenetics in the early nineties. For instance, epidemiological studies revealed a striking correlation between the food supply of grandfathers and an increased risk of diabetes and cardiovascular disease in their grandchildren. Since then, various reports suggested epigenetic inheritance in different organisms but the molecular mechanisms were unknown", says Nicola Iovino, corresponding author in the new study.

Epigenetics between the generations

He and his team at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg, Germany used fruit flies to explore how epigenetic modifications are transmitted from the mother to the embryo. The team focused on a particular modification called H3K27me3 that can also be found in humans. It alters the so-called chromatin, the packaging of the DNA in the cell nucleus, and is mainly associated with repressing gene expression.

The Max Planck researchers found that H3K27me3 modifications labeling chromatin DNA in the mother's egg cells were still present in the embryo after fertilization, even though other epigenetic marks are erased. "This indicates that the mother passes on her epigenetic marks to her offspring. But we were also interested, if those marks are doing something important in the embryo", explains Fides Zenk, first author of the study.

Inherited epigenetic marks are important for embryogenesis

Therefore the researchers used a variety of genetic tools in fruit flies to remove the enzyme that places H3K27me3 marks and discovered that embryos lacking H3K27me3 during early development could not develop to the end of embryogenesis. "It turned out that, in reproduction, epigenetic information is not only inherited from one generation to another but also important for the development of the embryo itself", says Nicola Iovino.

When they had a closer look into the embryos, the team found that several important developmental genes that are normally switched off during early embryogenesis were turned on in embryos without H3K27me3. "We assumed that activating those genes too soon during development disrupted embryogenesis and eventually caused the death of the embryo. It seems, virtually, that inherited epigenetic information is needed to process and correctly transcribe the genetic code of the embryo", explains Fides Zenk.

Implications for the theory of heredity and human health

With these results the study by the Max Planck researchers is an important step forward and shows clearly the biological consequences of inherited epigenetic information. Not only by providing evidence that epigenetic modifications in flies can be transmitted down through generations, but moreover by revealing that epigenetic marks transmitted from the mother are a fine-tuned mechanism to control gene activation during the complex process of early embryogenesis.

The international team in Freiburg is convinced that their findings have far-reaching implications. "Our study indicates that we inherit more than just genes from our parents. It seems to be that we also get a fine-tuned as well as important gene regulation machinery that can be influenced by our environment and individual lifestyle. These insights can provide new ground for the observation that at least in some cases acquired environmental adaptations can be passed over the germ line to our offspring", explains Nicola Iovino. Further, since the disruption of epigenetic mechanisms may cause diseases such as cancer, diabetes and autoimmune disorders, these new findings could have implications for human health."

My comment: All change in organisms is based on epigenetic regulation of existing biological information OR loss of it. Random mutations and selection have no role in biodiversity. We can observe several fine tuned mechanisms that point to Intelligent Creator. The theory of evolution is a major heresy. Don't get misled.

2017/08/17

Different DNA structures exquisitely fine tune the activity and expression of genes

Complex biological structures are able to perform the myriad intricate and elaborate functions of the human body

https://www.nibib.nih.gov/news-events/newsroom/new-imaging-technique-overturns-longstanding-textbook-model-dna-folding

Excerpt: "How can six and half feet of DNA be folded into the tiny nucleus of a cell? Researchers funded by the National Institutes of Health have developed a new imaging method that visualizes a very different DNA structure, featuring small folds of DNA in close proximity. The study reveals that the DNA-protein structure, known as chromatin, is a much more diverse and flexible chain than previously thought. This provides exciting new insights into how chromatin directs a nimbler interaction between different genes to regulate gene expression, and provides a mechanism for chemical modifications of DNA to be maintained as cells divide. The results will be featured in the July 28 issue of Science.

For decades, experiments suggested a hierarchical folding model in which DNA segments spooled around 11 nanometer-sized protein particles, assembled into rigid fibers that folded into larger and larger loops to form chromosomes. However, that model was based on structures of chromatin in vitro after harsh chemical extraction of cellular components.
 
Now, researchers at the Salk Institute, La Jolla, California, funded by the NIH Common Fund, have developed an electron microscopytechnique called ChromEMT that enables the 3D structure and packing of DNA to be visualized inside the cell nucleus of intact cells. Contrary to the longstanding text book models, DNA forms flexible chromatin chains that have fluctuating diameters between five and 24 nanometers that collapse and pack together in a wide range of configurations and concentrations.

The newly observed and diverse array of structures provides for a more flexible human genome that can bend at varying lengths and rapidly collapse into chromosomes at cell division. It explains how variations in DNA sequences and interactions could result in different structures that exquisitely fine tune the activity and expression of genes.

“This is groundbreaking work that will change the genetics and biochemistry textbooks,” remarks Roderic I. Pettigrew, Ph.D., M.D., director of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), which administered the grant. “It’s an outstanding example of how constantly improving imaging techniques continue to show the true structure of everything from neuronal connections in the brain to the correct visualization of gene expression in the cell. It reveals how these complex biological structures are able to perform the myriad intricate and elaborate functions of the human body.”

“We identified a fluorescent small molecule that binds specifically to DNA and can be visualized using advanced new 3D imaging methods with the electron microscope,” explained Clodagh O’Shea, Ph.D., the leader of the Salk group, associate professor and Howard Hughes Medical Institute Faculty Scholar. “The system enables individual DNA particles, chains and chromosomes to be visualized in 3D in a live, single cell. Thus, we are able to see the fine structure and interactions of DNA and chromatin in the nucleus of intact, live cells.”

Dr. O’Shea’s team included collaborators from the University of California, San Diego, and the National Center for Microscopy and Imaging Research, San Diego.

The researchers believe their discovery dovetails with their research on how tumor viruses and cancer mutations change a cell’s DNA structure and organization to cause uncontrolled cell growth. It could enable the design of new drugs that manipulate the structure and organization of DNA to make a tumor cell ‘remember’ how to be normal again or impart new functions that improve the human condition.

“To see the human genome in in all of its 3D glory is the dream of every biologist. Now, we are working to design probes that will allow us to also see the proteins that bind to the DNA to turn genes on and off. We will then be able to view an actual gene in action,” concluded O’Shea."

My comment: Do you think scientists are able to create a regulatory system, where 3D structure affects accurately gene activity and expression? How is this kind of regulatory system done? Think about all of those complex factors needed for that kind of system to function. 3D genome provides an interesting epigenetic mechanism that might explain several types of alterations occurring in organisms due to nutrition, climate, stress, toxicants etc. Gene sequences don't determine traits. Life is not driven by gene sequences. Genes are driven by lifestyle. Don't get lost. 

2017/08/16

Biological information is compressed in an astonishing way

How much does weigh the dna of all 'species' in the world?


http://www.madsci.org/posts/archives/1999-06/928784618.Mb.r.html

"The human genome is about 3 x 109 basepairs long, which would weigh about 40 pg (picograms: 1 pg = 10^-12 grams) per genome. Human cells are diploid, i.e. each contains two copies of the genome, so the nuclear DNA from a human cell would weigh about 80 pg."
 
The human DNA with epigenetic layers weighs about 10^-10 g, i.e., 100 pg. There are some ten thousands of basic groups of organisms in the world, but let's assume the number of species to be one million, so the estimate does not go too low. Thus, the total genome of all organisms in the world weighs about 0.0001 g. The mosquito weight is about 2.5 mg and its proboscis weighs approximately 1/25 of the total mosquito weight. This weight can accommodate the genetic information of all organisms in the world.

This kind of hyper efficient way to pack massive amounts of biological information into a minimal space tells about God's intelligence. 

2017/08/13

Breakthrough device heals organs with a single touch

Tissue healing by microRNA induced epigenetic stem cell reprogramming

https://www.sciencedaily.com/releases/2017/08/170807120530.htm

Excerpt: "Researchers at The Ohio State University Wexner Medical Center and Ohio State's College of Engineering have developed a new technology, Tissue Nanotransfection (TNT), that can generate any cell type of interest for treatment within the patient's own body. This technology may be used to repair injured tissue or restore function of aging tissue, including organs, blood vessels and nerve cells.

Results of the regenerative medicine study published in the journal Nature Nanotechnology.

"By using our novel nanochip technology, injured or compromised organs can be replaced. We have shown that skin is a fertile land where we can grow the elements of any organ that is declining," said Dr. Chandan Sen, director of Ohio State's Center for Regenerative Medicine & Cell Based Therapies, who co-led the study with L. James Lee, professor of chemical and biomolecular engineering with Ohio State's College of Engineering in collaboration with Ohio State's Nanoscale Science and Engineering Center.

Researchers studied mice and pigs in these experiments. In the study, researchers were able to reprogram skin cells to become vascular cells in badly injured legs that lacked blood flow. Within one week, active blood vessels appeared in the injured leg, and by the second week, the leg was saved. In lab tests, this technology was also shown to reprogram skin cells in the live body into nerve cells that were injected into brain-injured mice to help them recover from stroke.
 
"This is difficult to imagine, but it is achievable, successfully working about 98 percent of the time. With this technology, we can convert skin cells into elements of any organ with just one touch. This process only takes less than a second and is non-invasive, and then you're off. The chip does not stay with you, and the reprogramming of the cell starts. Our technology keeps the cells in the body under immune surveillance, so immune suppression is not necessary," said Sen, who also is executive director of Ohio State's Comprehensive Wound Center.

TNT technology has two major components: First is a nanotechnology-based chip designed to deliver cargo to adult cells in the live body. Second is the design of specific biological cargo for cell conversion. This cargo, when delivered using the chip, converts an adult cell from one type to another, said first author Daniel Gallego-Perez, an assistant professor of biomedical engineering and general surgery who also was a postdoctoral researcher in both Sen's and Lee's laboratories.

TNT doesn't require any laboratory-based procedures and may be implemented at the point of care. The procedure is also non-invasive. The cargo is delivered by zapping the device with a small electrical charge that's barely felt by the patient.

"The concept is very simple," Lee said. "As a matter of fact, we were even surprised how it worked so well. In my lab, we have ongoing research trying to understand the mechanism and do even better. So, this is the beginning, more to come."

Researchers plan to start clinical trials next year to test this technology in humans, Sen said."

My comment: How does this tissue healing method work? Certain microRNA molecules, such as miR-27a and miR-24 target several pluripotency associated factors in the cell. This means that these microRNA molecules affect the differentiation state of the cell and reset it. It means they remove or clear the epigenetic information layers of the cell making them pluripotent stem cells that are able to differentiate into any cell type. RNA molecules carried by exosomes in cells of target tissue direct the re-differentiation procedure of stem cells. So, changing the identity of the cells has nothing to do with mutations.

By the way, did you know that similar microRNAs can be found in human sperm, for example? And they have the same function; to reset the differentiation state of embryonic cells. This procedure is done in perfect timing.

Reprogramming of cells point to Intelligent Design and Creation. Don't get lost.

2017/08/09

Rapid increase in human disease-causing genomic mutations

The Annual increase of disease-causing genomic mutations was about 20,000

http://www.hgmd.cf.ac.uk/ac/index.php

The number of disease-causing genomic mutations in the human genome rose to just 208,368. Thus, annual growth has been around 20,000. And modern science does not know any beneficial random mutations. Similar genetic degradation occurs in all organisms.  

Evolution really does not happen.

2017/08/06

Embryos won’t use anything else but parent's genes

Extending human genome seems to be impossible

https://www.statnews.com/2017/08/02/crispr-designer-babies/

Excerpt: "Creating “designer babies” with a revolutionary new genome-editing technique would be extremely difficult, according to the first U.S. experiment that tried to replace a disease-causing gene in a viable human embryo.

Partial results of the study had leaked out last week, ahead of its publication in Nature on Wednesday, stirring critics’ fears that genes for desired traits — from HIV resistance to strong muscles — might soon be easily slipped into embryos. In fact, the researchers found the opposite: They were unable to insert a lab-made gene.

Biologist Shoukhrat Mitalipov of Oregon Health and Science University, who led the first-of-its-kind experiment, described the key result as “very surprising” and “dramatic.”
 
The “external DNA” provided to fertilized human eggs developing in a lab dish “was never used,” he told STAT. The scientists excised a mutated, heart-disease-causing gene from the embryos — a gene that came from sperm used to create them through in vitro fertilization — and supplied them with a healthy replacement. But every single one of the 112 embryos ignored it. Instead, they copied the healthy gene from their mother and incorporated that into their genome to replace the father’s.

“This is the main finding from our study,” Mitalipov said: Embryos’ natural preference for a parent’s gene “is very strong, and they won’t use anything else.”

The discovery suggests that opportunities for disease prevention are more limited than scientists assumed and that enhancement — giving a days-old embryo “better” genes — is unlikely to succeed, at least with current methods. Genetic tinkering can, however, eliminate a “bad” gene that an embryo got from one parent and replace it with a “good” gene from the other parent. And the experiment showed for the first time in a large number of embryos that this can be done efficiently and without harming other genes."

My comment: Genes are no drivers or controllers. Gene sequences don't determine traits. Scientists are not able to extend human genome by inserting more genetic material into embryonic cells. But due to rapid degeneration of the human genome, scientists are in a hurry to develop accurate gene editing techniques, by which they can remove faulty sections by letting the cell repair damages or by inserting healthy genetic material from parent's genome. Interesting is that the embryonic cells don't accept insertion of external genes. So, scientists can forget the idea of designer babies. And they can forget the idea of human induced evolution.