Cell Compacts Its DNA when Starved of Oxygen or Nutrients

저자：   업로드：2015-11-12  조회수：

    For cells to function normally, large parts of their DNA structure have to be open and accessible so molecules that read genetic code can produce instructions for making proteins. Now, researchers have discovered that when cells are starved of oxygen or nutrients, they compact their DNA, making it difficult for these normal functions to continue.

    The latest peek inside the DNA bunker has been taken by scientists of the Institute of Molecular Biology (IMB) in Mainz. They took advantage of a technique called single-molecule localization microscopy, a form of super-resolution light microscopy that uses blinking dyes that bind to DNA to enable researchers to define the location of individual molecules in cells. With this technique and other methods, the IMB scientists gained new insight into DNA’s hunkered-down state, which typically occurs when cells are deprived of adequate blood supply, during episodes of heart attack and stroke, for example.

    The scientists presented their results November 5 in the journal Genome Biology, in an article entitled, “A transient ischemic environment induces reversible compaction of chromatin.”

    “Short-term oxygen and nutrient deprivation of the cardiomyocyte cell line HL-1 induces a previously undescribed chromatin architecture, consisting of large, chromatin-sparse voids interspersed between DNA-dense hollow helicoid structures 40–700 nm in dimension,” wrote the authors. “The chromatin compaction is reversible, and upon restitution of normoxia and nutrients, chromatin transiently adopts a more open structure than in untreated cells.”

    The scientists found that the compacted state of chromatin reduces transcription, whereas the open chromatin structure induced upon recovery provokes a transitory increase in transcription. Confirming these results, the scientists determined that condensed chromatin exhibits an increased resistance to digestion with DNAseI compared with chromatin in untreated cells and, additionally, that the mobility of linker histone H1, as estimated by fluorescent recovery after photobleaching (FRAP), is significantly reduced by oxygen and nutrient deprivation.

    “When you have a stroke, when you have a heart attack, this is likely to be what's happening to your DNA," explained George Reid, Ph.D., one of the IMB scientists and a senior author of the Genome Biology paper. "Now we know that this is what's going on, we can start to look at ways of preventing this compaction of DNA."

    According to the IMB scientists, the extent and reversibility of chromatin compaction induced by oxygen and nutrient deprivation suggests that the impact of ischemia could be constrained by targeting biochemical events that are required for chromatin condensation. To some extent, these events are already being targeted in preclinical studies. For example, animal studies are evaluating the potential benefits of inhibiting histone deacetyla

이전：Cells May Rest, but Not Histones

다음에：Researchers Zero In on Cellular Stress Link to Heart Disorders