Home > Author > Nessa Carey
41 " John Gurdon spent around fifteen years, starting in the late 1950s, demonstrating that in fact nuclei from specialised cells are able to create whole animals if placed in the right environment i.e. an unfertilised egg "
― Nessa Carey , The Epigenetics Revolution
42 " There is increasing evidence that at least some of the targeting of epigenetic modifications can be explained by interactions with long ncRNAs. Jeannie Lee and her colleagues have recently investigated long ncRNAs that bind to a complex of proteins. The complex is called PRC2 and it generates repressive modifications on histones. PRC2 contains a number of proteins, and the one that interacts with the long ncRNAs is probably EZH2. The researchers found that the PRC2 complex bound to literally thousands of different long ncRNA molecules in embryonic stem cells from mice13. These long ncRNAs may act as bait. They can stay tethered to the specific region of the genome where they are produced, and then attract repressive enzymes to shut off gene expression. This happens because the repressive enzyme complexes contain proteins like EZH2 that are capable of binding to RNA. "
43 " Most of the time these enzymes will only add a methyl group to a C that is followed by a G. C followed by G is known as CpG. "
44 " There’s an amazing family of genes, called HOX genes. When they’re mutated in fruit flies (Drosophila melanogaster) the results are incredible phenotypes, such as legs growing out of the head14. There’s a long ncRNA known as HOTAIR, which regulates a region of genes called the HOX-D cluster. Just like the long ncRNAs investigated by Jeannie Lee, HOTAIR binds the PRC2 complex and creates a chromatin region which is marked with repressive histone modifications. But HOTAIR is not transcribed from the HOX-D position on chromosome 12. Instead it is encoded at a different cluster of genes called HOX-C on chromosome 215. No-one knows how or why HOTAIR binds at the HOX-D position. There’s a related mystery around the best studied of all long ncRNAs, Xist. Xist ncRNA spreads out along almost the entire inactive X chromosome but we really don’t know how. Chromosomes don’t normally become smothered with RNA molecules. There’s no obvious reason why Xist RNA should be able to bind like this, but we know it’s nothing to do with the sequence of the chromosome. The experiments described in the last chapter, where Xist could inactivate an entire autosome as long as it contained an X inactivation centre, showed that Xist just keeps on travelling once it’s on a chromosome. Scientists are basically still completely baffled about these fundamental characteristics of this best-studied of all ncRNAs. "
45 " Twelve ncRNAs were tested, and in seven cases the scientists found the result shown in the right-hand panel of Figure 10.2. This was contrary to expectations, because it suggests that about 50 per cent of long ncRNAs may actually increase expression of neighbouring genes, not decrease it "
46 " Developmental processes become much easier to visualise if we think of them as never-ending circles rather than in straight lines. "
― Nessa Carey , Junk DNA: A Journey Through the Dark Matter of the Genome
47 " Let’s imagine DNA as a giant zip, where each tooth is one of the four letters of the genetic code. "
― Nessa Carey , Hacking the Code of Life: How gene editing will rewrite our futures
48 " The epigenetics revolution is underway. "
49 " One possible explanation would be that quite randomly the twin with schizophrenia had spontaneously developed mutations in genes in certain cells, for example in the brain. This could happen if the DNA replication machinery had malfunctioned at some point during brain development. These changes might increase his or her susceptibility to a disorder. This is theoretically possible, but scientists have failed to find much data to support this theory. "
50 " A single miRNA can influence many of these differently spliced versions simultaneously. Alternatively, a single miRNA can also influence quite unrelated proteins that are encoded by different genes but have similar 3′ UTR sequences. This can make it very difficult to unravel exactly what a miRNA is doing in a cell, as the effects will vary depending on the cell type and the other genes (protein-coding and non-protein-coding) that the cell is expressing at any one time. "
51 " This relies on the second component which is a protein that can act like a pair of molecular scissors, cutting across the DNA double helix. These scissors don’t cut randomly; they don’t just flail across the genome. Instead, they only cut where the guide molecule has inserted itself into the DNA. "
52 " The phrase ‘gene editing’ is used to refer to the technology that has developed since 2012, which permits scientists to alter genomes with exceptional precision and ease. "
53 " gene editing leaves no molecular trace at all. "
54 " In conditions where there are an abnormal number of chromosomes, for example, it won’t just be protein-coding genes that change in number. There will also be abnormal production of ncRNAs (large and small). Because miRNAs in particular can regulate lots of other genes, the effects of disrupting miRNA copy numbers may be very extensive. "
55 " In this manifestation of gene editing, it is impossible to distinguish between an organism that was edited by scientists in the laboratory and a naturally occurring variant with the same change in the same letter. "
56 " However, there are two things we can say quite firmly. One is that human and chimp proteins are incredibly similar. About a third of all proteins are exactly the same between us and our knuckle-dragging cousins, and the rest differ only by one or two amino acids. Another thing we have in common is that over 98 per cent of our genomes don’t code for protein. This suggests that both species use ncRNAs to create complex regulatory networks which govern gene and protein expression. But there is a particular difference which may be very important between chimps and humans. This lies in how ncRNA is treated in the cells of the two species. "
57 " The rationale was quite simple. If the gene editing resulted in a genetic change that does or could occur in nature, then there’s no need for the regulators to get involved. "
58 " miRNAs play major roles in control of pluripotency and control of cellular differentiation. ES cells can be encouraged to differentiate into other cell types by changing the culture conditions in which they’re grown. When they begin to differentiate, it’s essential that ES cells switch off the gene expression pathways that normally allow them to keep producing additional ES cells (self-renewal). There is a miRNA family called let-7 which is essential for this switch-off process "
59 " About 99% of the DNA in a human cell is in the nucleus. Half of this is inherited from your mother and half from your father. But about 1% of the human genome is in 1,000 to 2,000 tiny subcellular structures called mitochondria. "
60 " But some mRNAs can take a long time to break down in a cell. This means that when a stem cell starts to differentiate, there will be a period when it still contains many of the stem cell mRNAs. Happily, when the stem cell starts differentiating, it switches on a new set of miRNAs. These target the residual stem cell mRNAs and accelerate their destruction. This rapid degradation of the pre-existing mRNAs ensures that the cell moves into a differentiated state as quickly and irreversibly as possible "