Epigenetic Mechanism Tunes Brain Cells

Regular replacement of histones in human and murine neurons is required for neuronal plasticity, a study shows.

By | July 2, 2015


When a cell divides and copies its DNA, it also makes copies of histones, the proteins that spool DNA and regulate gene expression. Since most neurons don’t typically divide, scientists have long thought that their histones also remain stagnant. A study published in Neuron  yesterday (July 1) is now challenging that view, showing that neurons in mice and in humans switch out old histones for new ones, and that this process is important for brain plasticity.

“These are very exciting results, creating a new front in the field of chromatin biology,” study coauthor Ian Maze, a neurobiologist at the Icahn School of Medicine at Mount Sinai, said in a statement.

Maze and colleagues at Mount Sinai and Rockefeller University examined levels of a histone variant called H3.3 that is known to turn over in other cells, even when those cells are not dividing. They found that H3.3 accumulates with age in neurons from mouse brains and post-mortem human brain tissue. The team used a technique called 14C/12C bomb pulse dating, which takes advantage of the high levels of radioactive carbon released into the atmosphere during World War II, to determine that humans replace H3.3 throughout their lives.

To further elucidate the turnover process, the researchers fed mice food laced with a radioactive isotope of lysine that could be detected in recently-made histone, and found that mice housed in mentally stimulating environments containing toys and wheels had more H3.3 turnover in their hippocampi, MedicalXpress reports. The scientists also demonstrated a relationship between histone replacement and neuronal plasticity in human and mouse cell lines.

“Histone turnover, shown through our work with H3.3, is essential for the behavior of brain cells,” Maze said. “Furthering our understanding of how the brain works, learns, forms new memories and reacts to changes in the environment can help us to find new ways to treat neurodegenerative diseases and mental illness.”

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Avatar of: James V. Kohl

James V. Kohl

Posts: 481

July 3, 2015

See also: Every amino acid matters: essential contributions of histone variants to mammalian development and disease

RNA-mediated amino acid substitutions link nutritional epigenetics to pharmacogenomic testing via the conserved molecular mechanisms of biophysically constrained protein folding chemistry in all genera.

Fixation of the amino acid substitutions occurs in the the context of the physiology of reproduction.

That fact refutes all, or nearly all, representations of mutation-driven evolution by correctly linking ecological variation to ecological adaptations via experimental evidence of biologically-based cause and effect during life-history transitions, such as this one: Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults

There are too many examples of what happens via a single base pair change linked to a single nutrient-dependent amino acid substitution for serious scientists to continue reporting results in the terms used by evolutionary theorists.

This claim has been fully supported during the past two decades of scientific progress:

“These are very exciting results, creating a new front in the field of chromatin biology,” study coauthor Ian Maze, a neurobiologist at the Icahn School of Medicine at Mount Sinai, said in a statement.

So has this claim from the molecular epigenetics section of our 1996 Hormones and Behavior review.

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.


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