Biochemical controls: histone role in cell functions (Introduction)

by David Turell , Sunday, September 01, 2024, 16:28 (83 days ago) @ David Turell

Continuing research:

https://knowablemagazine.org/content/article/living-world/2024/histones-do-a-lot-more-t...

"Every second, as we breathe, sleep, eat and go about our lives, millions of biochemical reactions are happening in our cells. Among the hurly burly of chemical exchanges are ones that attach small carbon molecules onto (or remove them from) proteins, fats, DNA and more. Adding or taking away these small molecules is essential for many reactions that enable cells to survive, grow and divide.

"Perhaps the most interesting and well-studied target of these additions and subtractions lies within the bustling nucleus, where various enzymes attach or remove two small molecules — methyl groups and acetyl groups — onto histones, the protein spools around which our DNA is wrapped.

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"...accumulating evidence shows that this is only part of the story. Although putting methyl and acetyl groups on histones is closely linked with activity of nearby genes in some places in the genome, in many other regions it has no impact at all. This suggests that regulating gene activity is not the only function of these histone decorations — perhaps not even the main one.

"In fact, emerging research suggests that these modifications to histones have key roles in the cell’s biochemical processes — its metabolism — functioning as a way for the cell to deal with small carbon molecules that are produced during biochemical reactions.

"Researchers propose that for acetyl groups (made of two carbons, three hydrogens and one oxygen), the histones serve as a kind of bank or repository that the cell can draw on when it needs more acetyls for chemical reactions.

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"Histones were once viewed as mere structural scaffolding for genes: something that could keep dense folds of DNA strands in order. Then they were seen as involved in gene control — either facilitating or blocking the unfolding of DNA that enables it to be copied. Now, if the new research pans out, they will also prove to be deeply intertwined with the metabolic workings of the cell.

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"Tu also saw that when genes involved in cell growth were at their peak activity, this coincided with high numbers of acetyl groups stuck on their histones. And when the genes went silent in the next phase of the cell cycle, the acetyl groups went away. “That was very exciting,” Tu says.

"It was exciting because acetyl groups are produced by the mitochondrion — the cell’s power-generating organelle. Acetyl groups are used by the cell to make molecules like fatty acids that are used for energy or to build cell membranes. What seemed to be happening was that acetyls were serving as a signal from the mitochondrion to the cell nucleus that these were times of abundance, with lots of available energy and chemical building blocks. By sticking onto the histones, they were ramping up activity of genes involved in cell growth. It makes sense, after all, to grow and divide during times of plenty.

"Tu also saw signs that the acetyls on histones could also act as a bank — a source of energy for the cell to draw on when times became leaner. When cells were starved, he observed, the amount of an important chemical called acetyl-CoA — which is central in energy generation — decreased in the cell. To make energy, the cells consumed acetyl groups that had detached from the histones. The acetyl groups that remained were rearranged so that they would activate genes to produce more acetyl-CoA.

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"More evidence for a metabolic role of histones comes from a 2023 study in which University of Oxford biochemist Peter Sarkies and his colleague Marcos Francisco Pérez examined a whole host of different enzymes that all add methyl groups to histones.

"Each enzyme puts methyl groups on at a unique place on the histone — a floppy part called the histone tail. Depending on where the methyls are added, the effect can be associated with activated gene activity, suppressed gene activity or no change at all. Sarkies reasoned that, if one is simply trying to get methyl groups out of the way so that metabolism can proceed, what matters is the sum activity of all of these enzymes –– not any individual enzyme or a particular effect on a nearby gene.

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"The scientists also found that many of the methylating enzymes were under the influence of a gene called Rb known for its role in suppressing cancer (it is often mutated in cancer cells). This suggested to Sarkies that Rb plays a central role in increasing or decreasing the rate at which methyl groups are deposited on histones and thus regulating biochemical pathways and growth.

“'What we discovered is that the cell uses histone methylation not just to regulate genes, but to regulate metabolism,” Sarkies says."

Comment: a very long article which describes many other functions and their evolution from an Archaean form. Of course, this complexity supports the argument for a designer.