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A Single Change at Telomeres Controls the Ability of Cells to Generate a Complete Organism

posted by Fnord666 on Tuesday August 27 2019, @07:15AM   Printer-friendly
from the don't-misread-the-title dept.

upstart writes:

Submitted via IRC for SoyCow3196

A single change at telomeres controls the ability of cells to generate a complete organism

Pluripotent cells can give rise to all cells of the body, a power that researchers are eager to control because it opens the door to regenerative medicine and organ culture for transplants. But pluripotency is still a black box for science, controlled by unknown genetic (expression of genes) and epigenetic signals (biochemical marks that control gene expression like on/off switches). The Telomeres and Telomerase Group, led by Maria Blasco at the Spanish National Cancer Research Centre (CNIO), now uncovers one of those epigenetic signals, after a detective quest that started almost a decade ago.

It is a piece of the puzzle that explains the observed powerful connection between the phenomenon of pluripotency and telomeres—protective structures at the ends of chromosomes—a kind of butterfly effect in which a protein that is only present in telomeres shows a global action on the genome. This butterfly effect is essential to initiate and maintain pluripotency.

The DNA of telomeres directs the production of long RNA molecules called TERRAs. What the CNIO researchers found is that TERRAs act on key genes for pluripotency through the Polycomb proteins, which control the programs that determine the fate of cells in the early embryo by depositing a biochemical mark on the genes. The on/off switch that regulates TERRAs, in turn, is a protein that is only present in telomeres; this protein is TRF1, one of the components of the telomere-protecting complex called shelterin. The new result is published this week in the journal eLife.

Rosa María Marión et al. TERRA regulate the transcriptional landscape of pluripotent cells through TRF1-dependent recruitment of PRC2, eLife (2019). DOI: 10.7554/eLife.44656

Original Submission

 
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  • (Score: 0) by Anonymous Coward on Tuesday August 27 2019, @11:59PM (2 children)

    by Anonymous Coward on Tuesday August 27 2019, @11:59PM (#886504)

    Any citations for that hypothesis?

    Or do you mean trans-individual memory? In which case yes, I'm aware some epigenetic toggles (mostly methylation but iirc there's another form?) are passed parent to child.

  • (Score: 2) by Dr Spin on Wednesday August 28 2019, @10:46AM

    by Dr Spin (5239) on Wednesday August 28 2019, @10:46AM (#886725)

    No citations - its my own hypothesis.

    --
    Warning: Opening your mouth may invalidate your brain!

  • (Score: 2) by gringer on Saturday August 31 2019, @07:03PM

    by gringer (962) on Saturday August 31 2019, @07:03PM (#888289)

    Parroting something I wrote on reddit, try here. These seem to be fairly old theories:

    https://www.nature.com/articles/s41539-019-0048-y.pdf [nature.com]

    Holliday further emphasized that DNA methylation may not underlie the storage of all types of memory. For example, he noted that the DNA of Drosophila appeared to lack cytosine methylation, but fruit flies nevertheless exhibit long-term memory. Since the publication of Holliday’s paper, however, there have been reports of DNA methylation in Drosophila; this phenomenon appears to be associated primarily with development, but DNA methylation has now been documented in adult flies as well. Holliday’s hypothesis that DNA methylation might subserve memory has received striking confirmation during the past decade. Studies in mammals and invertebrates have documented roles for DNA methylation in the formation of a variety of forms of learning and memory. These studies have shown that inhibitors of DNA methyltransferase (DNMT) block the formation and/or consolidation of memory. In addition, extensive DNA methylation changes have been documented for hippocampal-dependent fear conditioning in the brains of mice and rats; theseinvolve both hypermethylation and hypomethylation (see below) of genes. Moreover, the pattern of DNA methylation changes alters over time, with some patterns apparently associated with long-term maintenance of memory, because they occur weeks after training.

    And a bit further on (note: RNA, not DNA, but the RNA trick doesn't work without DNA methylation):

    The strongest challenge to date to the synaptic plasticity hypothesis of memory storage comes from a recent study by Bédécarrats et al., who reported successful transfer of memory from a trained to an untrained animal via RNA injection.... Importantly, the sensitizing effect of the trained donor RNA, like tail shock-induced long-term sensitization, depended on an epigenetic change, DNA methylation: when the RNA injection was followed immediately by an injection of the DNMT inhibitor RG108, the behavioral enhancement was blocked.

    I'll admit to having an unpopular opinion that DNA methylation changes are changes of DNA, rather than a "punctuative seasoning" of the DNA. It's my expectation that as we discover more about DNA structure and the function of modifications, we'll see more things relating to DNA as a functional and dynamic chemical rather than just a static data store.

    --
    Ask me about Sequencing DNA in front of Linus Torvalds [youtube.com]