Epigenetics: microRNAs effect an integrative pathway

By: James V. Kohl | Published on: May 9, 2015

Global Developmental Gene Programing Involves a Nuclear Form of Fibroblast Growth Factor Receptor-1 (FGFR1)
Excerpt 1)

The accumulation of hypoglycosylated nuclear FGFR1 (nFGFR1) is stimulated by a variety of developmental signals, including various growth factors, hormones, and neurotransmitters as well as a reduction in cell contact. This is the reason that this pathway is referred to as integrative [1, 15].

Reported as:

Master orchestrator of the genome is discovered, stem cell scientists report

Summary: New research shows how a single growth factor receptor protein programs the entire genome. The study provides evidence that it all begins with a single “master” growth factor receptor that regulates the entire genome.

My comment: The “master” growth factor receptor appears to be nutrient-dependent, and it can be linked from microRNAs to cell type differentiation via the integrative pathway that links ecological variation to the physiology of reproduction and to nutrient-dependent ecological adaptations in all genera.
Excerpt 2)

Mutations of the Fgfr1 gene interfere with gastrulation, as well as with development of the neural plate and neural crest, central nervous system, and somites by affecting the expression of diverse genes [3–6] and microRNAs [7, 8] that control development. These observations firmly place Fgfr1 at the top of the developmental hierarchy.

My comment: These observations are not historical, which means they are not linked to the fossil record. Instead, these observations place mutations below the bottom of the developmental hierarchy because they perturb the biophysically constrained chemistry of protein folding.
The perturbed protein folding links viral microRNAs from entropic elasticity to genetic entropy. Viruses and viral microRNAs have not been linked to increasing organismal complexity and biodiversity via the fossil record or any other non-observational approach to ecological adaptation. Viruses have been linked to pathology. For contrast, nutrient-dependent microRNAs link the microRNA/messenger RNA balance to the nutrient-dependent pheromone-controlled physiology of reproduction in species from microbes to man via the biophysically constrained chemistry of nutrient-dependent feedback loops linked from chromatin loops to fixation of RNA-mediated amino acid substitutions in the context of the physiology of reproduction.
See: Feedback loops link odor and pheromone signaling with reproduction and New database links regulatory DNA to its target genes
See also: Inching toward the 3D genome

…the nucleome structure changes as cells age, differentiate, and divide, and researchers want to understand how and why.

Researchers have linked nucleome structure to Fgfr1. They need only link nutrient-dependent microRNAs to the Fgfr1 gene to clarify the link to virus-driven mutations of the Fgfr1 gene from the accumulation of viral microRNAs and the link from viruses to pathology.
Re: Master orchestrator of the genome is discovered, stem cell scientists report

The idea that a single protein could bind thousands of genes and then organize them into a hierarchy, that was unknown,” Stachowiak said. “Nobody predicted it.”

My comment: Now that this fact is known, it can be linked to the fact that RNA-directed DNA methylation and RNA-mediated amino acid substitutions link the epigenetic landscape to the physical landscape of DNA in the organized genomes of all genera via the fixation of the amino acid substitutions that occurs in the context of the physiology of reproduction. See for instance: 1) From Fertilization to Adult Sexual Behavior and my invited review of nutritional epigenetics: 2) Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems. For example, substitution of the achiral amino acid glycine in the gonadotropin releasing hormone (GnRH) decapeptide links atoms to ecosystems in all vertebrates. Claims that any vertebrate species evolved from another species have not been supported by experimental evidence of biologically based cause and effect. Given experimental evidence that Global Developmental Gene Programing Involves a Nuclear Form of Fibroblast Growth Factor Receptor-1 (FGFR1), it seems more unlikely that theorists will link any of their claims about mutations from ecological variation to ecological adaptations. For contrast see:
Excerpt (from 1):

Yet another kind of epigenetic imprinting occurs in species as diverse as yeast, Drosophila, mice, and humans and is based upon small DNA-binding proteins called “chromo domain” proteins, e.g., polycomb. These proteins affect chromatin structure, often in telomeric regions, and thereby affect transcription and silencing of various genes (Saunders, Chue, Goebl, Craig, Clark, Powers, Eissenberg, Elgin, Rothfield, and Earnshaw, 1993; Singh, Miller, Pearce, Kothary, Burton, Paro, James, and Gaunt, 1991; Trofatter, Long, Murrell, Stotler, Gusella, and Buckler, 1995). 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.

Abstract (from 2):

This atoms to ecosystems model of ecological adaptations links nutrient-dependent epigenetic effects on base pairs and amino acid substitutions to pheromone-controlled changes in the microRNA / messenger RNA balance and chromosomal rearrangements. The nutrient-dependent pheromone-controlled changes are required for the thermodynamic regulation of intracellular signaling, which enables biophysically constrained nutrient-dependent protein folding; experience-dependent receptor-mediated behaviors, and organism-level thermoregulation in ever-changing ecological niches and social niches. Nutrient-dependent pheromone-controlled ecological, social, neurogenic and socio-cognitive niche construction are manifested in increasing organismal complexity in species from microbes to man. Species diversity is a biologically-based nutrient-dependent morphological fact and species-specific pheromones control the physiology of reproduction. The reciprocal relationships of species-typical nutrient-dependent morphological and behavioral diversity are enabled by pheromone-controlled reproduction. Ecological variations and biophysically constrained natural selection of nutrients cause the behaviors that enable ecological adaptations. Species diversity is ecologically validated proof-of-concept. Ideas from population genetics, which exclude ecological factors, are integrated with an experimental evidence-based approach that establishes what is currently known. This is known: Olfactory/pheromonal input links food odors and social odors from the epigenetic landscape to the physical landscape of DNA in the organized genomes of species from microbes to man during their development.


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