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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
(Score: 2) by gringer on Wednesday August 28 2019, @03:52AM (2 children)
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)
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
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.
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]