The Xist lncRNA interacts directly with SHARP to silence transcription through HDAC3was reported as:

How an RNA gene silences a whole chromosome

Summary: “Researchers have discovered how an abundant class of RNA genes, called lncRNAs can regulate key genes. By studying an important lncRNA, called Xist, the scientists identified how this RNA gathers a group of proteins and ultimately prevents women from having an extra functional X-chromosome — a condition in female embryos that leads to death in early development. These findings mark the first time that researchers have uncovered the mechanism of action for lncRNA genes.”

My comment: We reported this link to RNA-mediated cell type differentiation in our 1996 Hormones and Behavior review of pheromone-controlled sex differences in cell types.

Excerpt: “Genomic-imprinting is also manifest in specific parts of the X-inactivation region’s related XIST gene. Here male- and female-specific methyl-group patterns participate in X-inactivation in females and also in the preferential inactivation of the paternal X in human placentae of female concepti (Harrison, 1989; Monk, 1995).”

My comment: Others who are reporting on how the epigenetic landscape is linked to the physical landscape of DNA have now begun to make rapid progress by linking the biophysically constrained chemistry of nutrient-dependent RNA-mediated protein folding to cell type differences. However,  they lag behind attempts to integrate what is known about physics, chemistry, and conserved molecular epigenetics. They appear to be too specialized and their specialization has left them with no model of biologically-based cause and effect.

The model must link viral microRNAs from entropic elasticity and the anti-entropic effects of nutrient-dependent microRNAs to genome organization. Although a few others may realize the requirement to link microRNAs and messenger RNAs from RNA-directed DNA methylation to RNA-mediated amino acid substitutions that differentiate cell types, reports are scattered across disciplines.

See for examples: Properties and kinetics of microRNA regulation through canonical seed sites in the Journal of RNAi Gene Silencing and see Nuclear compartmentalization of odorant receptor genes, published in PNAS, which was edited by Linda B. Buck, an American biologist best known for her work on the olfactory system. She was awarded the 2004 Nobel Prize in Physiology or Medicine, along with Richard Axel.

Linda B. Buck is also the senior author of Feedback loops link odor and pheromone signaling with reproduction.

The fact that many researchers still do not understand how the biophysically constrained chemistry of nutrient-dependent pheromone-controlled cell type differentiation occurs in species from microbes to man attests to the inability of most scientists to look beyond their speciality areas and help those who are Combating Evolution to Fight Disease by learning how metabolic networks and genetic networks are epigenetically linked by RNA-mediated events.

See also: RNA and dynamic nuclear organization.

Co-author Michael Guttman is the senior author of The Xist lncRNA interacts directly with SHARP to silence transcription through HDAC3. Co-author John Rinn also co-authored ‘Oming in on RNA–protein interactions

Excerpt: “…the interactions between pre-mRNA and proteins fine-tune alternative splicing in a manner that can gradually create new protein functionalities without the need to create additional genes and without affecting existing proteins [4-6].”

In our 1996 review we (TB) 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…”

The only reason I know for the delay in learning about how RNA-mediated amino acid substitutions link the epigenetic landscape to the physical landscape of DNA is that evolutionary theorists have continued to tout pseudoscientific nonsense for nearly two more decades. See, for example: Mutation-Driven Evolution for comparison to my review article, which was published on the same day in 2013: Nutrient-dependent/pheromone-controlled adaptive evolution: a model.

See also my invited review of nutritional epigenetics: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems

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