Researchers: Epigenetics helps cells remember who they are

_{Denyse O'Leary

December 20, 2016

Epigenetics, Intelligent Design, News}

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From science writer Philip Ball at Physics:

How does a liver cell remember that it’s a liver cell when it replicates? A cell’s identity is determined in part by small molecules that bind to chromosomes at specific locations. Now researchers have devised a model that seems to explain how these so-called epigenetic patterns are sustained across generations of cells. The model connects the epigenetic marking of genes with the three-dimensional structure of DNA as it is folded up inside chromosomes. It leads to a mechanism for patterns of markings to be repaired if they are disturbed by events such as gene replication.

Epigenetic markings are small molecules added onto parts of chromosomes that may act as genetic switches, silencing some genes and turning on others, so that cells become different types—liver, muscle, or heart cells, for example. Chromosomes are made of chromatin fibers, which are linear DNA molecules looped around cylindrical histone proteins, forming a “string of pearls.”

…

There is experimental evidence that in real cells the proteins that write epigenetic marks are recruited by proteins that read the same mark. This protein association can help to sustain epigenetic memory via a positive feedback loop: even if some marks get erased, the presence of others in the same region will encourage the erased marks to be written back again. More.

What we need now is a good hard dose of genetic fundamentalism. Genes rule. Period. 😉

See also: Epigenetics: What China’s government famine can teach us about inherited starvation effects

and

Epigenetic change: Lamarck, wake up, you’re wanted in the conference room!

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Comments

Silver Asiatic, In the film "Amadeus" they show Mozart terminally ill in bed dictating the notes corresponding to the symphonic music he had composed and could play in his mind. The music existed in Mozart's mind before it was given to us in material form, so that it could be symbolically written on paper and played by musicians. The great Italian musician Salieri that worked for the emperor was very upset because God had unfairly given Mozart divine music and then had let Salieri live to enviously suffer while listening to Mozart's compositions. That reminds of the last part of the first chapter of Paul's first epistle to the Christians in Corinth.Dionisio_{December 28, 2016
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Silver Asiatic,
We might think of a musician who improvises on the original melody and structure of the piece.
Yes, that's a good analogy. We could think of different renditions of the same song. Always within the music framework rules, which the musician understands well. Now, since you brought up the music topic, did you watch the film "Amadeus"?Dionisio_{December 28, 2016
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D
That’s not changing the design but taking advantage of it.
That's a good way to put it. We might think of a musician who improvises on the original melody and structure of the piece.Silver Asiatic_{December 28, 2016
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Silver Asiatic, #26 addendum New functional specified information may be added along the way during the design implementation, but always within the context of the original design principles and rules. That's not changing the design but taking advantage of it.Dionisio_{December 27, 2016
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ayearningforpublius @28 & @29: Very insightful comments and very interesting links. Thank you.Dionisio_{December 27, 2016
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Dionisio @ 20 Your comment on the ballet struck a note with me. Following are some of my similar observations: _________________________________ Some of the fundamentals of Darwinian Evolution, as I understand it are: The complexities of life we see all around us, and within us are assembled from the bottom up in a Natural Selection process which chooses beneficial mutations among a long series of such changes, while allowing less beneficial changes to wither away, or perhaps allowed to remain as flotsam or “junk.” The resulting “designs” we see from such a process are merely illusions, the appearance of design … not actual design as we see in all of the human artifacts we dwell among such as the automobile and computers. Evolution is said to be without purpose, without direction and without goals. What we may see as purpose, direction and goals are simply the result of the workings of natural processes – simply illusions of and the appearance of design, ___________________ So then why do we see purpose, direction and goals at every level of life – from the cellular level, to the systems level to the completed body plan? We see purpose in the various machines and structures within each of several trillion cells in our bodies. We see the Kinesin motor transporting cargo from one place on the cell to another. We see the marvel of DNA which, coupled with other cellular components, represents not only a massive mass storage capability, but also represents a type of blueprint package defining all aspects of the end product body. This DNA package also contains what can be described as a complete set of “shop travelers” which, much like a manufacturing process, provides step by step instructions and bills of materials for the manufacture of the myriad parts making up the completed human body – bones, hair, brain, liver, eye, nose … and more. And each of these subunits exhibits purpose — specific purpose. What is finally assembled as an arm and hand for example, takes on a myriad of functional purposes such as accurately throwing a baseball, playing a musical instrument such as a violin and cradling a new born baby. Each of our vital organs play specific and necessary roles in keeping our body alive and functioning – there are goals and purpose expressed in each and every one of our body parts. What we see and experience in the finished goal directed and purposeful human body is beautifully expressed in many ways, such as when we witness a magnificent choral and orchestral performance such as Handel’s Messiah. What we experience in that concert hall is not an illusion — it is real and is the culmination of a multitude of designs, both in the natural as well as the realm of human intelligence and ingenuity. Se also -- https://ayearningforpublius.wordpress.com/2016/08/05/the-not-so-intelligent-designer/ayearningforpublius_{December 26, 2016
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Dionisio @22 (and elsewhere) As a long term software developer back when the .NET Framework and C# was introduced (early 2000s as I recall) I became very passionate about the whole package, and especially the Team System. I was able to advocate and introduce .NET into our system in some of our subsystems. If you are interested, here is a link to the system I worked on for many years as a software developer. https://www.cubic.com/Portals/0/Files/Tech-Center/11741_004%20Air%20Combat%20Training%20br_lr.pdf In earlier days, during a particularly tough project at the Yuma MCAS range, it settled into my mind and soul that complex systems such as what I was working through, and also the complexities of life -- just don't happen by chance. Evolution, in the Darwinian sense, simply does not happen, has not happened, and will not happen. I (and I assume others here) would be interested in your systems and software background. Best regardsayearningforpublius_{December 26, 2016
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It appears to me that the next opportunity for research would be to find a way of removing these epigenetic markers from the DNA of a particular non-stem cell, and that being accomplished, seeing if that causes it to revert back to stem cell functionality.EvilSnack_{December 25, 2016
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Silver Asiatic, Yes, that's a good point. Thank you for bringing it up here. One doesn't have to make changes to the design if it is done right from the start. A good design would include any necessary features to allow for complex adaptations to future changes in the requirements. The engineering software I worked on was actually designed from the start to allow major adjustments (adaptations) to the application requirements and conditions. In fact that's one of the main features that made it very appreciated by many engineers who used the software in their projects. The users in one state could adjust the program to their own standards, which could differ radically from other states. The software included relatively easy tools for the users to modify its functioning. That flexibility was a game changer. Basically it looked as if they had purchased completely different programs that were made for their particular requirements and conditions. But in reality it was just one software that had been designed to be transformed into more specialized applications for specific needs. Actually, at the annual conferences we saw users showing very "unexpected" applications of the software. Back then we were the ones "surprised" to see the clever applications the users presented at the conferences. Sometimes we asked them "how did you do it?" or "what program did you use?" :) However, compared to the built-in adaptive framework observed within the biological systems, the software we made looks like a Lego toy for toddlers, to say it nicely. Incomparable. Two separate leagues. That's why we see the biology research papers often say "unexpected" and "surprised". :)Dionisio_{December 24, 2016
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D <blockquote.Nonmaterial idea of the system first, its material implementation second. Do you see the point? Yes, but you have a non-material component that is active during the implementation. That's what I was getting at. You can decide and even make changes to the design.Silver Asiatic_{December 24, 2016
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Silver Asiatic @21 & @23::
Interesting analogy. We do applaud the actors. And we don’t know if the proteins that do this work are doing something more than following the programming of nature either. Maybe they have a certain kind of awareness — or in humans share some part of the consciousness of the person.
Then you should know well that the whole electronic system (computers, servers, peripheral devices, etc.) that is operated through various levels of software controls that are coded using different levels of programming languages and the whole nine yards, all that stuff is completely void of any consciousness or awareness. The entire teleology and intelligence is in the mind of those who created all that electronics+software paraphernalia. In my case the main idea of the software for engineering design that my employer developed and distributed, the main idea of all that was in an engineer's mind before I was instructed to implement it in the computers. The big picture of the still nonexistent system was in my supervisor's mind before he explained it to my and my colleagues so that we could develop and implement his idea. The idea preceded the actual system that many engineers used later. My boss explained how it works before it even existed. We programmers coded software to implement an existing nonmaterial idea in the material realm. The brilliant engineer who had that idea explained it to us the analysts and programmers and gave us instructions for development, implementation and testing of his idea. Nonmaterial idea of the system first, its material implementation second. Do you see the point? Are you still going to play the role of your politely dissenting interlocutors and pretend that you don't get it? :) Biology research is discovering amazingly elaborate information-processing systems with built-in frameworks (like .NET) that are conducive to robust adaptation mechanisms implemented in those systems in order to act in response to thermodynamic noise and biochemical stress associated with environmental changes or other surrounding conditions. The biological systems are designed top-down but ongoing research is mostly bottom-up, hence they constantly are surprised that while some outstanding questions get answered new ones are raised. Unending Revelation of the Ultimate Reality (UROTURE). That's all!Dionisio_{December 24, 2016
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D
Are you familiar with software development for engineering design? Have you heard of the .NET Framework?
Yes and yes.Silver Asiatic_{December 23, 2016
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Silver Asiatic, You sound a little like David Chalmers with his universally shared consciousness concept (assuming I understood it) trying to explain what he himself calls "the hard problem of consciousness". Are you familiar with software development for engineering design? Have you heard of the .NET Framework? [https://msdn.microsoft.com/en-us/library/zw4w595w.aspx]Dionisio_{December 23, 2016
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Dionisio
The teleology is not in a protein that recruits another in order to do something specific, but in the designed functional choreography where those proteins are just actors playing their part out of a general script.
Interesting analogy. We do applaud the actors. And we don't know if the proteins that do this work are doing something more than following the programming of nature either. Maybe they have a certain kind of awareness -- or in humans share some part of the consciousness of the person.Silver Asiatic_{December 23, 2016
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Silver Asiatic, #19 addendum The teleology is not in a protein that recruits another in order to do something specific, but in the designed functional choreography where those proteins are just actors playing their part out of a general script. Watch classical ballet. For example in this season The Nutcracker. Pay attention to every move and the background music. All in synch. At the end the prima ballerina and the entire ensemble get a long standing ovation. But what about the orchestra underneath and its director? What about the choreographer? And what about the composer? Who started the whole thing? Does the standing audience remember that while applauding so euphorically?Dionisio_{December 23, 2016
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Silver Asiatic @17:
The teleological language makes it difficult to understand this also.
Well, in many cases it's written inaccurately, because the real teleology is in the mind of the conscious designer, not in the designed biological systems or their biochemical components. However, from your ID perspective both explicit and implicit teleology in the biology papers should sound like music to your ears. :) However, to your politely dissenting interlocutors the same teleology should sound unacceptably senseless and even repulsive. Poor things. Too bad. It all depends on the reader's point of view. :)Dionisio_{December 23, 2016
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BA77 - thanks for your Christmas greeting! Wishing you the very best also.Silver Asiatic_{December 22, 2016
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Dionisio Thanks for your interesting reply.
Also transcription, post-transcriptional modifications, translation, post-translational modifications, etc. may be affected by external physicochemical stressing.
I wonder if wd400 accepts that or not. Wd? The paper seemed to say that non-genetic markers were created and sustained by proteins and then used to switch on and off certain genes which cause cells to have one specific function or another:
Epigenetic markings are small molecules added onto parts of chromosomes that may act as genetic switches, silencing some genes and turning on others, so that cells become different types—liver, muscle, or heart cells, for example.
Again, I can't envision the mutation/selection pathway that created this network. I would think changes would have to happen simultaneously for the process to continue to function.
There is experimental evidence that in real cells the proteins that write epigenetic marks are recruited by proteins that read the same mark. This protein association can help to sustain epigenetic memory via a positive feedback loop: even if some marks get erased, the presence of others in the same region will encourage the erased marks to be written back again.
The teleological language makes it difficult to understand this also. Proteins "recruit" other proteins in order to complete a task of reading markers? The presence of markers "encourage the erased markers to be written back again"? As it stands, it's not very clear.Silver Asiatic_{December 22, 2016
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BA77, Thank you for your message and for many interesting comments you have posted in this site. May you have a joyful Christmas season. Rev. 22:21Dionisio_{December 22, 2016
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Silver Asiatic @13: Your persistent inquiring approach to scientific questions is commendable and encouraging. I like it. I see your disappointment with certain phrases we encounter quite often in the biology papers. You would like to know "how mutation and selection created those relationships." Please, keep in mind that I'm simply a student wannabe. I'm interested in a few aspects of biology, but still my knowledge of this science is below basic. The more I know, more I have to learn. Sometimes, when I feel overwhelmed by the increasing volume of information I want to review and by the frustrating feeling of not being able to understand as much as I'd like to, I remember that "yesterday all my troubles seemed so far away" but "now it looks as though they're here to stay". :) In fact, I've questioned the need to struggle with so many difficult to understand issues. I'd rather go fishing. :) However, it's too late for me now. There's no escape. This biology studying has become so addictive that it has hindered my daily activities, including my work in an important project that is far behind schedule. But this is a trap almost like the Eagles' Hotel California, except that in my case it's good. Every time I've run for the door I've realized that I can't leave. I'm stuck with this studying. :) All that disclaimer said, let's go back to your interesting request: You would like to know "how mutation and selection created those relationships." I believe biology presents myriad of mutations of all kinds, specially neutral and deleterious, but maybe sometimes advantageous at the micro-evolutionary (adaptation) level. Had we remained in Eden none of that would have been an issue. But we are far from Eden. Unfortunately human history is messy at best. We have messed up ourselves beyond recovery. Just look around and most importantly, look at ourselves. Can epigenetic markers get affected by external factors? I think so. Also transcription, post-transcriptional modifications, translation, post-translational modifications, etc. may be affected by external physicochemical stressing. Again, we were made to be in Eden. Biological systems are amazingly delicate and robust at the same time, but beyond certain limit, things go nuts beyond recovery. We wanted to do it our way and here we are. We deserve a bigger mess than we are in. God has been merciful and gracious to us after all our bizarre attitude. If I were God I would have wiped it all and started anew. But He didn't, because He knew it. No surprise at all. That's why He had the exit door included in the design right before it got implemented. Recently an interesting paper that links diet with cancer was posted in the thread "Mystery at the heart of life". You may want to take a look at it. Regarding selection, I think that's a wide concept. Perhaps some micro-evolution or adaptation is associated with particular combinations of changes that are not fatal and surrounding conditions. In the thread "A third way of evolution?" see the post @1090. That's in a nutshell how evo-devo research should approach the macro-evolution conundrum if they want to make it acceptable to any seriously thinking person. I don't recall seeing a case where mutation and selection create something new that's not just a variation of what was there before. They modify existing things producing new variations of existing things and so on. That's why the built-in adaptive framework within biological systems is referred to as evolution by the academic establishment, or at least many within it. Perhaps gpuccio can find time to expand on this. His insightful explanations are always welcome and helpful here. Then you can start a new discussion sequel that readers can enjoy. Agree?Dionisio_{December 22, 2016
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Silver Asiatic and Dionisio, While in college, wd400 did not study for very important tests on a certain day in several different classes. Instead of leaving all the test answers blank, wd400 just proceeded to bluff his way through all of the exams. All answers wd400 gave were along this line, 'the question you asked is inappropriate because you just don't truly understand the subject'. Whereas in all his engineering, physics and math classes wd400 obviously failed all his exams big time and flunked his courses, in his evolutionary biology class, the Darwinian Professor was so impressed by wd400's unmitigated chutzpah that wd400 received an A+ and, in addition, was given a free ride on a scholarship from there on out. And there you have the rest of the story as to how the world was blessed with yet another Darwinian know-it-all. :) Merry Christmas all: Selah - Light of the Stable https://www.youtube.com/watch?v=Xy5y9SkiwcEbornagain77_{December 22, 2016
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Dionisio @ 11 We haven't been given an adequate answer on how mutation and selection created those relationships. But if you find one in your research, please post it. I'm getting a little tired of hearing that such things are "far from understood". :-)Silver Asiatic_{December 22, 2016
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wd First, thanks for responding. It seems, at time, as in this case, that you're just dismissive. The paper is narrowly focused on one aspect. But for us, it points to the bigger story. Yes, science will go on, and will continue to ignore our concerns on these matters. But eventually the truth will win out. The neo-Darwinian mechanism cannot explain the origin of this phenomenon.Silver Asiatic_{December 22, 2016
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SA, check this out:
One of the most important problems in development is how epigenetic domains can be first established, and then maintained, within cells. Epigenetic modifications are biochemical marks that form patterns along chromosomes and regulate gene expression. The epigenetic patterning of chromosomes enables cellular differentiation, while leaving the underlying DNA sequence unchanged. How these patterns are established and then maintained across cell division is far from understood, however. […] an outstanding question is how the epigenetic landscape is established in the first place—and how this can be reset de novo after each cell division.
A Polymer Model with Epigenetic Recolouring Reveals a Pathway for the de novo Establishment and 3D Organisation of Chromatin Domains Davide Michieletto, Enzo Orlandini, Davide Marenduzzo doi: https://doi.org/10.1101/058933 Phys. Rev. X 6, 041047 http://biorxiv.org/content/early/2016/10/23/058933.full.pdf http://journals.aps.org/prx/abstract/10.1103/PhysRevX.6.041047#fulltext

[emphasis added] Did you see this? How these patterns are established and then maintained across cell division is far from understood an outstanding question is how the epigenetic landscape is established in the first place—and how this can be reset de novo after each cell division. work in progress... stay tuned. But tomorrow ongoing research will make new discoveries that will shed more light on the elaborate molecular and cellular choreographies orchestrated within the biological systems, thus answering some of the outstanding questions while raising new ones. One problem is that research is bottom-up but the biological systems were designed top-down. With every discovery the big picture is getting more difficult for your politely-dissenting interlocutors to explain. For you it's easy to explain: ID. Please, be nice to them! Show compassion with the losers! Be magnanimous in victory! :)Dionisio_{December 21, 2016
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Again, I'm not sure you read the paper. This is a computational model.wd400_{December 21, 2016
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SA, That's a rhetorical question you asked. You know the answer and you know that your politely-dissenting interlocutor doesn't. Please, be nicer. As the ultimate winners, we should be magnanimous toward the losers and show compassion to them. :) The best is yet to come. We ain't seen nothing yet.Dionisio_{December 21, 2016
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wd400 As you well know, we're interested here in the origin of such things. If you're saying that it has nothing to do with mutation, then how did it emerge?Silver Asiatic_{December 21, 2016
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Well, SA, I seriously wonder if you did read the paper. Has nothing to do with mutation, let alone mutational biases. The paper is fairly interesting, in that such a simple model can explain maintenance of the chromatin state. Not very relevant to News' confused war on basic genetics or your comment though.wd400_{December 21, 2016
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SA, I tip my hat to you buddy. You really do have a talent for imitating the politely dissenting interlocutors! Actually, you do it better than they usually do. :) However, you may also add their killer statement: "you don't understand evolution." which completely demoralizes the ID folks and their cousins. :) Oh, well. Whatever. Welcome to this world. :)Dionisio_{December 21, 2016
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Thanks, Dio. Interesting, yes. I'm a little disappointed that wd400 missed his cue though. I could take on his role until he arrives, at least for now:
How these patterns are established and then maintained across cell division is far from understood, however.
SA filling in for wd: "So called epigenetics is merely the same environmental pressures that cause mutational bias - already known for decades. I don't see what you find so interesting here. Did you guys even read the paper?"Silver Asiatic_{December 21, 2016
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