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

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


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  • (Score: 2) by Dr Spin on Tuesday August 27 2019, @08:16AM (9 children)

    by Dr Spin (5239) on Tuesday August 27 2019, @08:16AM (#885991)

    Anyone with half a brain and an understanding of the design of a Turing machine should realise that the telomeres are the equivalent of working storage for the main DNA equivalent of a program.

    --
    Warning: Opening your mouth may invalidate your brain!
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  • (Score: 2) by bzipitidoo on Tuesday August 27 2019, @10:22AM

    by bzipitidoo (4388) on Tuesday August 27 2019, @10:22AM (#886014) Journal

    I have often felt that biologists could use more training and knowledge of the principles of Computer Science. Computational Biology, if I understand it correctly, seems more about the use of computers for biological studies, than understanding the links and analogies between the principles of Universal Computation and Information Theory and the machineries around that, and biochemical machinery. Wonder how many biologists have not heard of cellular automata and Conway's Game of Life?

    Another example of the ignorance of biologists is their Newick tree format. It's okay, good enough to be useful, but it could be better. However, Computer Scientists haven't done much better at representing trees of the graph theoretical variety.

    It would be helpful if journalists would refrain from reporting every tiny advance as possibly, this time, the breakthrough that has unlocked the Secret of Life, and the Fountain of Youth and all that. But I suppose that would be like asking them not to breathe. I don't see that problem in this particular article. Way back in the day, some thought the discovery of DNA was It. Turned out, DNA was only the start, only an alphabet. That was like staring at compiled code without any idea of what it is other than that it makes computers go, and realizing there's letters in there, and those letters are '0' and '1'. And that was good enough to earn a Nobel Prize.

  • (Score: 5, Interesting) by gringer on Tuesday August 27 2019, @10:52AM (7 children)

    by gringer (962) on Tuesday August 27 2019, @10:52AM (#886024)

    The working storage of DNA is the methylation patterns. One hypothesis is that *our long-term memory* is encoded as methylation patterns.

    --
    Ask me about Sequencing DNA in front of Linus Torvalds [youtube.com]
    • (Score: 2) by Dr Spin on Tuesday August 27 2019, @08:39PM (3 children)

      by Dr Spin (5239) on Tuesday August 27 2019, @08:39PM (#886375)

      I was assuming the telomeres probably store the information relating to/involved in the replication process, assuming the operation of this
      process at the time the DNA strands are separated/re-paired is quite similar to the operation of a truing machine traversing the "infinite tape".

      I would expect Methylation to store information used once DNA is created, to control the creation of the proteins it codes for.

      Long term memory (accessible to the intellectual brain) is far more likely to be stored by creating/destroying dendrites in a similar manner
      to programming an FPGA. A lot of this is probably done by creating masses of dendrites and then allowing them to wither if not used
      (or not used under specific circumstances). This is like (anti-)fuse programmed PALs.

      I posit that the withering circumstances are created/enhanced during dream sleep - as it is generally a bad idea to reconfigure your CPU while running
      mission-critical software. (Dreams may be test-runs of the reprogrammed brain).

      Obviously, in all the above, I mean "analogous to", and not litteraly identical to.

      Disclaimer: I have worked in a neurology lab, but not in a position where I was allowed to probe live brains.

      Cue: https://www.youtube.com/watch?v=vNuVifA7DSU&t=111s [youtube.com]The Monster Mash

      --
      Warning: Opening your mouth may invalidate your brain!
      • (Score: 2) by gringer on Wednesday August 28 2019, @03:52AM (2 children)

        by gringer (962) on Wednesday August 28 2019, @03:52AM (#886624)

        I was assuming the telomeres probably store the information relating to/involved in the replication process, assuming the operation of this process at the time the DNA strands are separated/re-paired is quite similar to the operation of a truing machine traversing the "infinite tape".

        How do you propose they store this information? I was under the impression that they're composed almost entirely of tandem repeats (i.e. a unary number system), which doesn't seem like it would be able to encode anything beyond a simple counter. The infinite tape on a turing machine works because each position can be blank or marked, which is just enough variation to encode [almost] anything.

        --
        Ask me about Sequencing DNA in front of Linus Torvalds [youtube.com]
        • (Score: 2) by Dr Spin on Wednesday August 28 2019, @10:56AM (1 child)

          by Dr Spin (5239) on Wednesday August 28 2019, @10:56AM (#886726)

          If you are right about it being effectively nulls like tape leader, then I am wrong. Do you have any good evidence for your info?

          The telomere as data might only be valid/useful during the processes involved in RNA transcription or protein synthesis.

          The memory might be cleared after use, or even by use. It might mark sections of the DNA to be
          ignored or activated in some way during this process.

          Does methylation survive replication? I understood it would not (but I could be wrong).

          --
          Warning: Opening your mouth may invalidate your brain!
          • (Score: 2) by gringer on Saturday August 31 2019, @06:57PM

            by gringer (962) on Saturday August 31 2019, @06:57PM (#888286)

            If you are right about it being effectively nulls like tape leader, then I am wrong. Do you have any good evidence for your info?

            The DNA sequence derived from long nanopore reads on the fully-assembled telomere-to-telomere X chromosome:

            https://doi.org/10.1101/735928 [doi.org]

            The starting telomere is a near-perfect repeat of 'CCCTAA', repeated about 222 times. The ending telomere is a bit more variable, with 'GGGTTR' repeated about 240 times.

            Does methylation survive replication?

            Yes, methylation is transferred across during DNA replication. It is reset at meiosis, but some patterns are [somehow] preserved through meiosis as well despite the wiping at one stage of meiosis.

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