A Genetically Encoded Probe for Live-Cell Imaging of H4K20 Monomethylation
Excerpt (with my emphasis):
• A histone H4K20me1-specific live-cell probe, H4K20me1-mintbody, was developed.
• Dynamics and replication timing of Xi were visualized.
• Critical amino acids for the stability and/or folding of the mintbody were revealed.
H4K20me1 is most likely associated with the tight packing of a redundant (inactivated) female X chromosome (Xi) into heterochromatin. In a roundworm Caenorhabditis elegans model, Prof. Kimura and colleagues showed that the H4K20me1-mintbody could be used to monitor changes in H4K20me1 over the cell cycle and localization of dosage-compensated X chromosomes without disrupting cell function.
Also reported as: New Probe Detects Histone Modifications in Live Cells
Using genetic analysis and X-ray crystallography, the new work has also identified amino acids that are critical to the solubility and conformational stability of the H4K20me1-mintbody. Aberrant folding of the antibody fragments in the cellular cytoplasm usually causes solubility problems…
My comment: The nutrient-dependent pheromone-controlled cell cycle and localization of dosage-compensated X chromosomes links Max Tegmark’s claims about reorganized food and consciousness via the physiology of reproduction in Caenorhabditis elegans and other model organisms. The research results reported above link RNA methylation, learning and memory to RNA-directed DNA methylation via the addition of a methyl group or groups to histone H4 at the lysine 20 position (H4K20).
That energy-dependent change in methylation links biophysically constrained biologically-based cause and effect from yeast to humans. For instance, X-inactivation is closely linked from chromosomal rearrangements to sex differences in morphological and behavioral phenotypes in humans.
In the most recent report, they did not jump to humans from sex differences in the cell types of yeasts. Instead, they used the nematode, Caenorhabditis elegans as a link between the H4K20me1-mintbody and changes in methylation (i.e., H4K20me1) during the cell cycle at the cellular location of X-inactivated chromosomes. That’s how increasing orgaanismal complexity from yeasts to humans was again placed into the context of fixed RNA-mediated amino acid substitutions. I will reiterate this claim:
• Critical amino acids for the stability and/or folding of the mintbody were revealed.
They identifies the amino acids that are critical to the solubility and conformational stability of the H4K20me1-mintbody and critical to cell type differentiation in all cell types of all individuals of all species. They linked X-inactivation and chromosomal rearrangements from aberrant RNA-mediated protein folding biochemistry to the solubility problems caused by antibody fragments in the cellular cytoplasm and found a potential solution to the problem.
The problem they are trying to solve is different than mine. I gave up trying to solve the problem of how to explain the origin of sex differences in cell types in species from yeasts to humans by putting the explanation in terms that educated laypersons might understand. Even other scientists won’t admit to knowing anything about amino acid substitutions and cell type differentiation. Meanwhile, neo-Darwinian theorists are trying to bury any explanation for the origin of sex difference in cell types so that evolution via mutations and evolution can continue to be used as an explanation for all biodiversity, including the diversity in male and female gametes.
However, no experimental evidence of biologically-based cause and effect suggests that X-inactivation “evolved” via mutations and natural selection. And no experimental evidence of biologically-based cause and effect suggests that sex difference in cell types “evolved.”
These researchers overcame the challenges involved in explaining that fact to biologically uninformed theorists by evaluating the performance of antibody fragments in live cells. Unfortunately, explaining the complexity of X-inactivation to an educated layperson may not be possible — especially if that person thinks that sex differences “evolved” via mutations and natural selection.
Until many others accept the fact that nutrient energy-dependent fixation of RNA-mediated amino acid substitutions in the context of the physiology of reproduction is the link to all biodiversity and all cell type, most theorists will not be encouraged to learn more about how virus-driven energy theft is linked to all pathology. If they don’t understand biologically-based cause and effect, they are not likely to understand the need to link thermodynamic cycles of protein biosynthesis and degradation to the molecular mechanisms of biodiversity.
My comment: The epigenetic effects of nutrients on intracellular signaling and stochastic gene expression appear to enable ecological adaptations in the context of tightly controlled organism-level thermoregulation in mammals. Nutrient-dependent single amino acid substitutions and de novo protein biosynthesis exemplify the involvement of the seemingly futile thermodynamic control of intracellular and intermolecular interactions in microbes that result in stochastic gene expression.
Thermodynamically “futile” cycles of RNA transcription and degradation also are responsible for changes in pheromone production that enable accelerated changes in nutrient-dependent adaptive evolution controlled by the microRNA/messenger RNA (miRNA/mRNA) balance. Environmental cues, like those that signal the availability of glucose, appear to cause changes in the miRNA/mRNA balance that enable gene expression during developmental transitions required for successful nutrient-dependent reproduction in species from microbes to humans.
The facts about protein biosynthesis and degradation show that the thermodynamic cycles are nutrient energy-dependent and the facts link virus-driven energy theft to all pathology via conserved molecular mechanisms of biophysically constrained RNA-mediated protein folding chemistry that prevent one species from evolving into another via mutations and natural selection.
See for comparison: Broad histone H3K4me3 domains in mouse oocytes modulate maternal-to-zygotic transition
Active removal of broad H3K4me3 domains by the lysine demethylases KDM5A and KDM5B is required for normal zygotic genome activation and is essential for early embryo development. Our results provide insight into the onset of the developmental program in mouse embryos and demonstrate a role for broad H3K4me3 domains in MZT.
My comment: They must think everyone knows the importance of amino acid substitutions that link lysine to biophysically constrained energy-dependent cell type differention or from mutations to pathogy. There is no mention of lysine demethylases outside the context of nutrient energy-dependent RNA-mediated amino acid substitutions and no mention of lysine in the context of virus-driven energy theft. The only indication that they know how important the difference may be is their citation to: Trapnell, C. et al. Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat. Biotechnol. 28, 511–515 (2010).
The isoform switching is energy-dependent and RNA-mediated.
That fact was missing from this report of their work: Breakthrough genomics technique can be used to map epigenetic marks across the genome using fewer cells
Very soon after fertilization, the control of embryonic development shifts from pre-existing maternal gene products to the products of genes encoded by the early embryo (or zygote). This passing of the genetic baton, called the maternal-to-zygotic transition (MZT), is poorly understood because existing technologies have generally been too insensitive to capture the full scale of the epigenetic changes it entails across the zygotic genome.
See for comparison: From Fertilization to Adult Sexual Behavior
The Genome, positioning, timings. There are major structural differences between the X and Y chromosomes; e.g., centromeric aiphoid repeats sequences and distribution of heterochromatin (Graves, 1995; Wolfe et al., 1985). These structural differences correlate with sexually dimorphic chromosomal positioning within the nucleus and with male/female differences in replication timing of the active X, the inactive X, and the Y chromosomes, e.g., Boggs and Chinault (1994), Clemson and Lawrence (1996); Hansen, Canfield, and Gartler (1995). Increasingly the structure and timings within the nucleus are realized as contributing to gene expression regulation (Manders, Stap, Strackee, van Driel, and Aten, 1996; Stein, Stein, Lian, van Wijnen, and Montecino, 1996).
My comment: Our next section title was Molecular distance and the one after that was Molecular epigenetics. In the section on molecular epigenetics, we wrote:
Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation in at least two species, Drosophila melanogaster and Caenorhabditis elegans (Adler and Hajduk, 1994; de Bono, Zarkower, and Hodgkin, 1995; Ge, Zuo, and Manley, 1991; Green, 1991; Parkhurst and Meneely, 1994; Wilkins, 1995; Wolfner, 1988). That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes.
We did not link any aspect of RNA-mediated cell type differentiation from natural selection and evolution to sex differences in cell types or differences in somatic cell types. Why not? Because no experimental evidence suggests ecological variation can be linked to ecological adaptation via anything except energy-dependent fixation of RNA-amino acid substitutions in the context of the physiology of energy-dependent reproduction. All aspects of nutrient-dependent pheromone-controlled reproduction have been repeatedly linked from feedback loops to all biodiversity in all living genera. See: Feedback loops link odor and pheromone signaling with reproduction
The molecular basis of this learning mechanism could be searched for in model organisms showing epigenetic inheritance.
Zika virus damaged DNA is an example of how quickly one insect species can ecologically adapt to a virus that is transmitted to the humans with unrepaired DNA . The damage is manifested as changes in craniofacial morphology and brain development in the context of one base pair change and one amino acid substitution in the virus compared to failed ecological adaptation in primates.
Dobzhansky (1973) tried to put that fact into the context of primate ecological adaptation.
…the so-called alpha chains of hemoglobin have identical sequences of amino acids in man and the chimpanzee, but they differ in a single amino acid (out of 141) in the gorilla (p. 127).
See also: Combating Evolution to Fight Disease
The evolutionary biologist Theodosius Dobzhansky famously noted that “nothing in biology makes sense except in the light of evolution,” but perhaps, too, “nothing in evolution makes sense except in the light of biology.” Although the latter might be an exaggeration, an important gap is being filled by molecular understanding of the genesis of variation that confers the ability to evolve.
Crudely defined molecular mechanisms, however, have prevented a better understanding of genetic variants mediating sexually dimorphic expression.
My comment: All definitions of molecular mechanisms are useless to serious scientists who have linked energy-dependent changes from angstroms to ecosystems by starting with the sun’s biological energy.
See also: Plant RNAs Found in Mammals
My September 20, 2011 comment to the Scientist about this fact now appears to be attributed to an anonymous source
This important finding in mammals is predicted by an insect model in which the diet of the honeybee queen and her pheromones determine everything about the success of the hive including the neuroanatomy of worker bee brains.
The honeybee already serves as a model organism for studying human immunity, disease resistance, allergic reaction, circadian rhythms, antibiotic resistance, development, mental health, longevity, and diseases of the X chromosome. Included among these different aspects of eusocial species survival are learning and memory as well as conditioned responses to sensory stimuli, like food odors, and the social odors called pheromones. Thus, the honeybee model also predicts that the behavior of mammals will be influenced by food odors, nutrition, and pheromones to the same degree that chemical stimuli influence the behavior of every other species on the planet.
In mammals, of course, the epigenetic effects of pheromones in the mother’s milk are clearer, perhaps even to non-biologists.
See also: Sequencing Reveals Genomic Diversity of the Human Brain
Researchers examine the role of long interspersed element-1 retrotransposition in neuronal mosaicism.
My comment: Somatic mosaicism is nutrient energy-dependent and controlled by the physiology of reproduction in plants and animals.
Plant RNAs Found in Mammals (revisited)
MicroRNAs from plants accumulate in mammalian blood and tissues, where they can regulate gene expression.
Today’s comment: Energy-dependent changes in the microRNA/messenger RNA balance are linked to healthy longevity, and virus-driven energy theft is linked to all pathology via conserved molecular mechanisms.
See also: Abiogenesis: A Theory on The Origins of Life
My comment from last year:
See: Common origins of RNA, protein and lipid precursors in a cyanosulfidic protometabolism
Didn’t Sutherland’s group link the speed of light on contact with water to the de novo creation of nucleic acids and the biophysically constrained chemistry of nutrient-dependent RNA-mediated protein folding in accord with Schrodinger’s claim about the anti-entropic epigenetic effect of the sun?
The researchers also found that testosterone levels increased in men who had been given active light treatment. The average testosterone levels in the control group showed no significant change over the course of the treatment – it was around 2.3 ng/ml at both the beginning and the end of the experiment. However, the group given active treatment showed an increase from around 2.1 ng/ml to 3.6 ng/ml after two weeks.
See also: Chromatin: The structure of DNA (3)