A Reprogramming Histone

The scientist who pioneered cloning has found that a histone may act as a cellular reset button.  

By | October 29, 2012

Wikimedia, Toni BarrosIn the 1996 experiment that created the famous sheep Dolly, researchers swapped the nucleus of an unfertilized egg with that of a differentiated adult cell, which rebooted the adult nucleus to create the first cloned mammal. Now, John B. Gurdon of the Gurdon Institute in Cambridge and colleagues—who developed the technique and shared the Nobel Prize in Physiology or Medicine this year—have found that a histone variant, H3.3, plays a central role in transitioning an adult cell’s nucleus to a blank-slate capable of developing into any of the body’s cells.

"Manipulating the H3.3 pathway may provide a way to completely wipe a cell's ‘memory’ and produce a truly pluripotent cell,” geneticist Steven Henikoff, from the Fred Hutchinson Cancer Research Center, said in a press release. The results, published today (October 29) in Epigenetics & Chromatin, could have implications for regenerative medicine and other therapies, he added, which are beginning to use reprogrammed cells but still face difficulties, including low efficiency. “[It] suggests that chromatin is a sticking point preventing artificially induced reprogramming [from] being used routinely in the clinic."

For the experiment, Gurdon and colleagues implanted a nucleus from an adult mouse cell into an enucleated frog egg—similar to his first groundbreaking nuclear transfer experiment in 1962—and added fluorescently labeled histones, around which strands of DNA wrap, making certain genes available or unavailable for transcription.

"Using real-time microscopy it became apparent that from 10 hours onwards, H3.3 . . . became incorporated into the transplanted nucleus,” explained Gurdon in the press release. The team noted that H3.3’s placement in the DNA coincided with regions important for the regulation of key pluripotency genes, such as Oct4. The researchers also found that the nucleus wouldn’t reprogram without H3.3 present.

The finding suggests that this histone variant is necessary for global genome changes that control the cell fate, the authors wrote in the study.

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Avatar of: jeenious


Posts: 45

October 30, 2012

If information is not in any manner passed along from somatic cell experience to germline cells, by way of mutations exclusively confined to the germline cells (a Lammarckian occurrence) then it is only by transmittable mutations in parental germ cells, or invironmental influences on tranmission in sexual exchanges at conception that account for biological evolution of species.

The baffling thing is that no selection can occur between any trait, dominant or recessive or epigenetic, that is not present at time of conception. Errors in transcription at time of conception would tend astronomically to be mal-adaptive or cancerous.

Assuming that "information" about stress to the somatic cells of an organism, due to new inviornmental challenges or opportunities, cannot and is not brought to bear upon germline cells, we are forced to conclude that mad-adaptive changes occur uninfluenced by parental organisms' external invironment and are purely random, in that they do not influence any adaptation-appropriate program (i.e., DNA, RNA or epigenetic) changes whereby a species could adapt over successive generations.

If we seek to explain this away by attributing adaptation and evolution of a species to random chance, the statistical odds against appropriate adaptation are astronomically contrary to what obviously occurs over time in species. There HAS to be some adaptation-appropriate selection, and not merely selection among existing genes and epigenetic programming.

The process CANNOT be totally chaotic (random chance transcription errors or germ cell mutations, only).

May I live so long as to see the day when we understand how heritable, appropriate adaptations occur over successive reproductions.

Histones, no doubt, are involved. But the complexity of how the astronomically unlikely changes comprising biological evolution in sexually reproducing organisms remains a broad and complex mystery.

Avatar of: somey


Posts: 8

October 31, 2012

It is true DNA has both autocatalytic and heterocatalytic properties making it supremo of the cell.RNA by its primitive origin serves an equal purpose in some virus.Proteins with their largest variability capacity long thought and till that they are at the beck and call of nucleic acids-the idea must be modified.Proteins really control the structural organization and functioning patterns of nucleic acids.Who can say the type of protein to be synthesized in the ribosomes is governed ultimately by the proteins.

Avatar of: somey


Posts: 8

October 31, 2012

Thank You The World Scientist----You provide language for those who do not have.

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