DNA Loops Seem Too Short-Lived to Loom Large in Gene Expression
DNA has been known to form loops, and these loops have been thought to influence gene expression, recombination, and DNA repair. But according to a new study, DNA loops are rare and fleeting. Consequently, their functional role may need to be rethought
DNA has been known to form loops, and these loops have been thought to influence gene expression, recombination, and DNA repair. But according to a new study, DNA loops are rare and fleeting. Consequently, their functional role may need to be rethought.
DNA loops were subjected to live-cell imaging by researchers at the Massachusetts Institute of Technology (MIT). Using computational analysis to make sense of their observations, the researchers determined that in one stretch of the genome, fully formed loops exist for just 20–45 minutes, or about 3–6% of the time.
If the loop is only present for such a tiny period of the cell cycle and very short-lived, we shouldn’t think of this fully looped state as being the primary regulator of gene expression. Detailed findings from the study are appeared in the journal Science.
Besides establishing the rare and dynamic nature of full chromatin loops, the researchers found that partially extruded loops were present about 92% of the time. Indeed, by integrating their experimental data with polymer simulations, the researchers were able to quantify the relative extents of the unlooped, partially extruded, and fully looped states.
The researchers hypothesize that partial loops may play more important roles in gene regulation than fully formed loops. More than 90% of the time, there are some transient loops, and presumably what’s important is having those loops that are being perpetually extruded. The process of extrusion itself may be more important than the fully looped state that only occurs for a short period of time.
Using this technology, which combines new experimental and computational methods, can begin to approach other loops in the genome. The researchers plan to investigate the role of specific loops in disease. Many diseases, including a neurodevelopmental disorder called FOXG1 syndrome, could be linked to faulty loop dynamics. Also, they are now studying how both the normal and mutated form of the FOXG1 gene, as well as the cancer-causing gene MYC, are affected by genome loop formation.
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