Epigenetic Memory Changes during Embryogenesis

DNA is not just a static read-only memory (ROM) for coding proteins, but hosts dynamic random access memory (RAM) in the form of methylations and histone modifications for regulation of gene expression, cellular differentiation, learning and cognition, and who knows what else. The picture below depicts how rapidly the RAM aspect of DNA is changed during embryogenesis.

Many of the DNA methylation patterns are in non-coding repetitive regions. This suggests at least some of the roles of non-coding DNA are involved in supporting the complex epignomic memory in each cell.

Depicted below are changes in epigenetic methylation marks on the DNA in the stages of embryo development. The light green colors indicate epigenetic methylations and the darker blue colors indicate absence of epigenetic methylations. In boxes “a” through “l”, the bottom part is the DNA from the mother and the top part is the DNA from the father. Eventually the DNA from mom and dad mix in the 4 cells of box “m”.

Note how the epigenetic marks are erased from the parternal DNA first!

The depiction below shows how rapidly epigenetic changes happen even in time frames as short as hours. Each cell has a slightly different methylation pattern and hence each cell’s RAM has some unique information. If we consider that the human has 100 trillion cells and that each cell has 30 million potential methylation sites, the sum total of RAM memory implemented by epigenetic cytosine methylation alone is on the order of sextillions of bits of Shannon information. Like histones, DNA methylations can be written, erased and read.

When scientists inhibit epigenetic changes, the results are usually lethal. So we know the epigenetic component of the DNA is vital to life.

changes in methylation during embryogenesis

a–e, Anti-5-methylcytosine (MeC) immunofluorescence of mouse one-cell embryos. a, Zygote 3 h after fertilization with intense MeC labelling of both pronuclei (>10). Numbers in parentheses indicate the number of embryos analysed. b Paternal and maternal pronuclei at 6 h (>10). c, Undermethylated paternal pronucleus at 8 h (>20). The smaller female pronucleus remains methylated. d, Aphidicolin-treated one-cell embryo displaying demethylation of the male pronucleus (>20). e, First metaphase (>5). f–j, Controls. Anti-DNA immunofluorescence of one-cell embryos demonstrates that both chromatin sets are accessible to antibody molecules. f, 3 h (>5). g, 6 h (>5). h, 8 h (>5). i, Aphidicolin treatment (>5). j, First metaphase (2). k,l, MeC staining of two-cell embryos at 22 h (>20) (k) and 32 h (>20) (l) shows that the paternal and maternal compartments have different methylation levels. m, Four-cell embryo at 45 h (>10). The MeC-staining intensity of the maternal half of the nucleus is weaker than in two-cell embryos. Scale bar, 10 mum.

http://www.nature.com/nature/journal/v403/n6769/fig_tab/403501b0_F1.html#figure-title

http://www.nature.com/nature/journal/v403/n6769/fig_tab/403501b0_ft.html

356 thoughts on “Epigenetic Memory Changes during Embryogenesis

  1. I think I now understand why other blogsites can have so much profanity!
    Damn!!!!!!

  2. I seem to remember something along these lines going down in flames on Larry’s sandwalk.blogsite… Specifically random transposon jumping somehow being different in different tissues and that somehow that proved non-randomness and as a result also proved Intelligent Design.

    Can anybody help me out on this, not that it matters much, but I thought perhaps it was one of mregnor’s abominations on sandwalk.blogspot, maybe I am wrong.

    meanwhile – what is the “sal”-connection. I must be new here – what’s a “sal”?

    I will take one last stab at this.

    stcordova Before going any further with your metaphor, could you please explain what you think “epigenetics” really is?

    Your answer must somehow explain, what is being remembered and how. Understand that your answer CANNOT make reference to DNA methylation nor Histone acetylation because as Mark Ptashne explained, nucleosome modifications are by themselves not self-perpetuating and must therefore be considered peripheral to the epigenetic story. DNA methylation & Histone acetylation clearly are a result of “epigenetic memory” and not a cause.

    Your answer must be able to explain the difference between a mule and a hinny! Let me explain: A female hinny zygote is a diploid cell with two sets of chromosomes: one set from a donkey and another set from a horse; which BTW describes the exact same scenario for the female mule zygote. Those differential nucleosome modifications you keep on going on about, should be identical in both zygote scenarios, yet hinnies and mules are quite different due to “epigenetics”.

    So far I am convinced you are incoherent. I challenge you to prove me wrong. My challenge should not be too difficult given it can be answered by high school students.

    Please answer me directly without resorting to puerile evasionary tactics or rhetorical questions.

  3. stcordova,

    I think I see your point. I missed the word substrate where you are not talking about accessing DNA but simply looking at the read write behavior of histones where DNA is the substrate that holds them. In a prior discussion you talked about DNA as functioning as wire that separated binding proteins by enough space so they can operate to function. Very interesting ideas.

  4. Frankie:
    TomMueller,

    How did you/ they determine the transposon jumping was random?

    When you roll a pair of fair dice, how do you determine invisible pixies didn’t consciously manipulate the outcome?

  5. Adapa: When you roll a pair of fair dice, how do you determine invisible pixies didn’t consciously manipulate the outcome?

    Many gamblers are convinced they do. And the pixies work for the house.

  6. stcordova,

    How do you know there aren’t unique ways for each species. Yet another example again of UCAist non-sequiturs that go something like “they have a universal common ancestors, therefore species can’t implement epigenomes and genomes in different ways.”

    You are fond of paraphrases of positions which no-one holds. It must be the case, even on universal common ancestry, that ‘different species implement their genomes in different ways’. We observe them doing so.

    But what you seem to be hinting at is that the assumed common ancestry of different onions of the same genus is some kind of ‘science-stopping’ blocker to the possibility that they have different epigenetic requirements. But even if they were separately created I wouldn’t take that possibility seriously. Common ancestry isn’t the issue, epigenetic operation is. There are many, many genera containing more than one species. If it were the case that any such species pairs had significantly different epigenetic unrolling … don’t you think someone might have noticed?

  7. stcordova,

    Pseudogenes serve as nice miRNA decoys in a ceRNA regulatory schema. Transposons jump in somatic cells during neuron development to create diversity even though we don’t see them jump in the same way in the germ line.

    The key word missing there is SOME. SOME pseudogenes; SOME transposons. One cannot export the function of a subset of a class to the entire class. The term is ‘domestication’. Elements which do not as a rule have a positive effect on organismal fitness can evolve to do so. Individual instances, that is, not the entirety.

    Transposons are generally considered junk because of the nature of transposition (and the fact that there is wide variation within species).

    Some carnivores make very good pets.

  8. stcordova

    Coming soon to 24 hours by my clock… and still no reply except a puerile rhetorical question by Frankie.

    At what point is defeat conceded?

  9. TomMueller:
    stcordova

    Coming soon to 24 hours by my clock…and still no reply except a puerile rhetorical question by Frankie.

    At what point is defeat conceded?

    When the last king is strangled with the entrails of the last priest. Or, in this case, when all of the adherents are deceased and forgotten and all the scriptures turned to dust.

    Intelligent design creationism is and always has been a religious and political movement, never driven or supported by science. They will never concede defeat. The best we can hope for is to use elections and the courts to limit the damage they can do until they’re no longer a political threat.

  10. Adapa: When you roll a pair of fair dice, how do you determine invisible pixies didn’t consciously manipulate the outcome?

    Have you tried asking them?

  11. Neil Rickert: Do creationists ever concede defeat?

    You never do even though it has been proven that your position makes untestable claims and because of that is not science.

    Talk about total unawareness…

  12. TomMueller:
    stcordova

    Coming soon to 24 hours by my clock…and still no reply except a puerile rhetorical question by Frankie.

    At what point is defeat conceded?

    LoL! And I notice that you are too afraid to answer my question. However Spetner, 1997, 2014 makes the case that refutes your claim.

    Transposons carry within their sequence the coding for two of the enzymes required for it to move around. Please tell us how to test the claim that arose via stochastic processes- something scientific.

    Or else admit that your claims are puerile

  13. Patrick: When the last king is strangled with the entrails of the last priest.Or, in this case, when all of the adherents are deceased and forgotten and all the scriptures turned to dust.

    Intelligent design creationism is and always has been a religious and political movement, never driven or supported by science.They will never concede defeat.The best we can hope for is to use elections and the courts to limit the damage they can do until they’re no longer a political threat.

    LoL! ID doesn’t have anything to do with any religion. However given the untestable claims of your position we can easily see that it relies solely on faith.

    We will never concede defeat because you will never be able to test the claims of your position. And we understand that upsets you

  14. Frankie: ID doesn’t have anything to do with any religion

    Wedge document. And you knew that. You yourself used to write for a YEC website.

  15. This is proving to be an interesting experiment.

    Stcordova has evaporated without trace and Frankie persists in ignoring the original question by irrelevant posturing.

    Frankie, to quote you: “I asked first!”

    I wonder out loud; what is a reasonable time limit?

    At what point has stcordova implicitly conceded defeat to my question as posed, not Frankie’s preoccupation with my inquiry regarding the identity of preposterous posters on a different blog.site

  16. TomMueller,

    Again- Spetner 1997, 2014, along with what I posted. The sequence contains the coding for two of the enzymes required for it to move around (actually that is also covered in the referenced material).

    Just because we don’t understand what is happening isn’t any reason to classify them as random. You are assuming your conclusion.

  17. Here is the question one last time:

    I will take one last stab at this.

    stcordova Before going any further with your metaphor, could you please explain what you think “epigenetics” really is?

    Your answer must somehow explain, what is being remembered and how. Understand that your answer CANNOT make reference to DNA methylation nor Histone acetylation because as Mark Ptashne explained, nucleosome modifications are by themselves not self-perpetuating and must therefore be considered peripheral to the epigenetic story. DNA methylation & Histone acetylation clearly are a result of “epigenetic memory” and not a cause.

    Your answer must be able to explain the difference between a mule and a hinny! Let me explain: A female hinny zygote is a diploid cell with two sets of chromosomes: one set from a donkey and another set from a horse; which BTW describes the exact same scenario for the female mule zygote. Those differential nucleosome modifications you keep on going on about, should be identical in both zygote scenarios, yet hinnies and mules are quite different due to “epigenetics”.

    So far I am convinced you are incoherent. I challenge you to prove me wrong. My challenge should not be too difficult given it can be answered by high school students.

    Please answer me directly without resorting to puerile evasionary tactics as seems to be Frankie’s wont or rhetorical questions.

  18. I suggest a time limit before invoking an implied concession of defeat?

    Suggestions? … Another 24 hours perhaps?

  19. Frankie,

    Transposons carry within their sequence the coding for two of the enzymes required for it to move around. Please tell us how to test the claim that arose via stochastic processes- something scientific.

    Why is this relevant? Transposase could have been designed; this would not tell us anything about whether transposons act on their own account or as part of the greater organismal whole. Transposition is a close relative of viral infectivity. No-one claims viruses are doing their hosts a favour.

  20. Allan,

    Thank you for taking Frankie off my back!

    ITMT What would you suggest is a reasonable time limit for stcordova?

    Best regards

  21. TomMueller,

    Thank you for taking Frankie off my back!

    That is a task beyond my ability, I am afraid! There is, however, a handy little ‘Ignore Commenter’ button.

    ITMT What would you suggest is a reasonable time limit for stcordova?

    Sal has accepted points in the past; it’s not beyond the bounds of the possible that he will respond. Equally, I sometimes feel that some valid points have not even been read, let alone addressed. Either way, he does rather come and go.

  22. Allan Miller:
    Frankie,

    Why is this relevant? Transposase could have been designed; this would not tell us anything about whether transposons act on their own account or as part of the greater organismal whole. Transposition is a close relative of viral infectivity. No-one claims viruses are doing their hosts a favour.

    OK so you don’t have any justification for calling the actions of transposons random. And not all viruses are harmful. And some could very well be helpful.

  23. TomMueller,

    I have already answered the question about epigenetics. “Evolution in Four Dimensions” discusses the topic in detail

  24. Frankie:
    TomMueller,

    I have already answered the question about epigenetics. “Evolution in Four Dimensions” discusses the topic in detail

    Another puerile evasionary tactic!

    Please provide a brief and focused response to the question posed. One or two paragraphs should do. Otherwise I will have no more option but place you on IGNORE!

    Remember that your answer must also be able to explain the difference between a mule and a hinny!

  25. Frankie,

    OK so you don’t have any justification for calling the actions of transposons random.

    Changing the goalposts again. You brought up the enzymes involved in transposition, and said nothing about whether they were ‘random’ in operation. Just because they encode their own enzymes does not make their insertion positions surgical. They insert where they can.

    And not all viruses are harmful. And some could very well be helpful.

    Therefore what? All viruses are helpful? All transposons are helpful? We can just ignore the harmful ones because some aren’t?

  26. Apologies for sporadic visits, and thank you to all for pariticpating.

    TomMeuller:

    stcordova Before going any further with your metaphor, could you please explain what you think “epigenetics” really is?

    definition used by NIH researchers in the present day (though the term has evolved):

    Epigenetics is the study of heritable changes in gene expression or cellular phenotype, caused by mecahanisms other than changes in the underlying DNA sequence

    From the NIH Roadmap epigenetics project:

    http://www.roadmapepigenomics.org/overview

    Overview of the Roadmap Epigenomics Project

    Epigenetics is an emerging frontier of science that involves the study of changes in the regulation of gene activity and expression that are not dependent on gene sequence.

    For purposes of this program, epigenetics refers to both heritable changes in gene activity and expression (in the progeny of cells or of individuals) and also stable, long-term alterations in the transcriptional potential of a cell that are not necessarily heritable. While epigenetics refers to the study of single genes or sets of genes, epigenomics refers to more global analyses of epigenetic changes across the entire genome.

    The overall hypothesis of the NIH Roadmap Epigenomics Program is that the origins of health and susceptibility to disease are, in part, the result of epigentic regulation of the genetic blueprint. Specifically, epigenetic mechanisms that control stem cell differentiation and organogensis contribute to the biological response to endogenous and exogenous forms of stimuli that result in disease.

    The roadmap project focuses on cytosine methylation and histone modication as epigenetic factors. Additionally DNase hypersensitive sites and chromatin remodelling is studied. Some people include ncRNAs as part of epigenetics because they are transmitted down somatic cell line. I usually don’t include ncRNAs right now in the defintion of epigenetics, but the NIH may change their mind because ncRNAs floating around in the cell are often integrated with histone modifications.

    The ncRNAs are often phantom RNAs — about 10% of the RNA transcriptome has no direct analog in the DNA because of post transcriptional modification and who knows what else. The Fantom Transcriptome is starting to become a real issue because now we may have to have separate annotations for them.

  27. Understand that your answer CANNOT make reference to DNA methylation nor Histone acetylation because as Mark Ptashne explained,

    Ptashne is old school obsolete.

    From the NIH Roadmap project:

    http://www.roadmapepigenomics.org/

    The NIH Roadmap Epigenomics Mapping Consortium was launched with the goal of producing a public resource of human epigenomic data to catalyze basic biology and disease-oriented research. The Consortium leverages experimental pipelines built around next-generation sequencing technologies to map DNA methylation, histone modifications, chromatin accessibility and small RNA transcripts in stem cells and primary ex vivo tissues selected to represent the normal counterparts of tissues and organ systems frequently involved in human disease. The Consortium expects to deliver a collection of normal epigenomes that will provide a framework or reference for comparison and integration within a broad array of future studies. The Consortium also aims to close the gap between data generation and its public dissemination by rapid release of raw sequence data, profiles of epigenomics features and higher-level integrated maps to the scientific community. The Consortium is also committed to the development, standardization and dissemination of protocols, reagents and analytical tools to enable the research community to utilize, integrate and expand upon this body of data.

    The NIH Roadmap project is an almost 200 million dollar effort. They can define epigenetics for the rest of us with that sort of capital investment. I’m merely using their defintions not Ptachne’s — Ptachne obviously has a low opinion of NIH ENCODE and Roadmap.

  28. TomMueller,

    Well, I hope I’m not outing, but the s in stcordova stands for ‘Sal’.

    Nah, most people know who I am in TSZ circles, ever since I was the featured in the cover story of the prestigious scientific journal Nature in 2005 and on National TV in 2006. 🙂

  29. Speaking of that 2005 article in Nature that featured yours truly in the cover story:

    http://www.nature.com/nature/journal/v434/n7037/

    News Feature

    Nature 434, 1062-1065 (28 April 2005) | doi:10.1038/4341062a; Published online 27 April 2005

    Intelligent design: Who has designs on your students’ minds?

    Geoff Brumfiel1

    1. Geoff Brumfiel is Nature’s Washington physical sciences correspondent.

    Topof page
    Abstract

    The intelligent-design movement is a small but growing force on US university campuses. For some it bridges the gap between science and faith, for others it goes beyond the pale. Geoff Brumfiel meets the movement’s vanguard.

    For a cold Tuesday night in March, the turnout is surprisingly good. Twenty or so fresh-faced college students are gathered together in a room in the student union at George Mason University in Fairfax, Virginia, the state’s largest public university. They are there for the first meeting of Salvador Cordova’s Intelligent Design….

    I’m also listed at #81 on encyclopedia of American Loons, ahead of Sean Hannity:
    http://americanloons.blogspot.com/2010/10/81-salvador-sal-cordova.html

  30. Gollygeewillakers, look at the title of this 2013 book (emphasis mine):

    Epigenetic MEMORY and Control in Plants

    plant immunity epigenome

    And here is a hint how c-values can vary between individuals of a species and thus fine-tune regulation. Even though it doesn’t talk about C-value per say, a little out-of-the-box thinking can enlighten as to how this can be important for C-value issues:

    From a 2015 article:

    http://nar.oxfordjournals.org/content/early/2015/03/26/nar.gkv258.full

    Epigenetic regulation of intragenic transposable elements impacts gene transcription in Arabidopsis thaliana

    Genomes of higher eukaryotes, including plants, contain numerous transposable elements (TEs), that are often silenced by epigenetic mechanisms, such as histone modifications and DNA methylation. Although TE silencing adversely affects expression of nearby genes, recent studies reveal the presence of intragenic TEs marked by repressive heterochromatic epigenetic marks within transcribed genes. However, even for the well-studied plant model Arabidopsis thaliana, the abundance of intragenic TEs, how they are epigenetically regulated, and their potential impacts on host gene expression, remain unexplored. In this study, we comprehensively analyzed genome-wide distribution and epigenetic regulation of intragenic TEs in A. thaliana. Our analysis revealed that about 3% of TEs are located within gene bodies, dominantly at intronic regions. Most of them are shorter and less methylated than intergenic TEs, but they are still targeted by RNA-directed DNA methylation-dependent and independent pathways. Surprisingly, the heterochromatic epigenetic marks at TEs are maintained within actively transcribed genes. Moreover, the heterochromatic state of intronic TEs is critical for proper transcription of associated genes. Our study provides the first insight into how intragenic TEs affect the transcriptional landscape of the A. thaliana genome, and suggests the importance of epigenetic mechanisms for regulation of TEs within transcriptional gene units.

  31. stcordova: a little out-of-the-box thinking can enlighten as to how this can be important for C-value issues

    Could you explain your thinking here? It’s too far outside the box for me to see it.

  32. When I see the word “numerous” I want to know the percentages.

    Too often, numerous means thousands, which is a trivial percentage of nearly any genome.

    The problem is not that some non-coding DNA is functional. the problem is getting past 10 percent, for humans.

  33. stcordova: Epigenetic MEMORY and Control in Plants

    Sal, I edited your link as long URLs affect the display in smartphones. You can use Tinyurl or HTML tags (a href= etc).

  34. Sal, I edited your link as long URLs affect the display in smartphones. You can use Tinyurl or HTML tags (a href= etc).

    Thanks Alan.

    I’ll try to shrink the URL’s or provide hyperlinks.

  35. petrushka: The problem is not that some non-coding DNA is functional.

    If you read the paper, it isn’t even implied that the transposons are functional, and in fact the methylation is supposed to be a defense against the deleterious effects of insertions.

  36. To the extent that there is an epigenetic ‘memory’ encoded with a parallel frequency to DNA sequence, how is this memory supposed to stretch beyond one generation? Bearing in mind that there are two copies, one from each parent, of any methylated or unmethylated sequence, but an exponential number of ancestors whose ‘memories’ are vying for representation in the strictly binary resource of a diploid locus.

  37. John Harshman: If you read the paper, it isn’t even implied that the transposons are functional, and in fact the methylation is supposed to be a defense against the deleterious effects of insertions.

    If they are completely inert, what’s the point?

  38. petrushka: If they are completely inert, what’s the point?

    One possibility: to keep them from being transcribed and inserting somewhere else where they might cause a problem.

  39. Frankie,

    How am I changing the goalposts when that was my question from the beginning?

    No it wasn’t. You made two completely different points:

    Transposons carry within their sequence the coding for two of the enzymes required for it to move around. Please tell us how to test the claim that arose via stochastic processes- something scientific.

    This is about the origin of transposons. I queried the relevance of that to the discussion in hand, to which you responded:

    OK so you don’t have any justification for calling the actions of transposons random.

    This is about the action of transposons.

  40. but wait, wait, waaaaaaaaaaaiiiiiiiiiiiiit , dammit.

    Where’s Tom Mueller!!!

    Its been over 24 hours now and no rebuttal to the rebuttal of the rebutted but.

    Tom Mueller, down for the count !

  41. Allan Miller,

    The first question I raised was how did Tom know the movements were random. I then added the part of what a transposon is. And you don’t have any justification for calling their movements random

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