This holiday season, you may not be able to escape the big family dinner table, and the aunts and uncles that drink too much and bring up old arguments. But researchers at Temple University report that some genes can escape from the stranglehold of silencing that long noncoding RNAs (lncRNAs) impose. And they do it with the help of enhancers that drive the chromatin to form acrobatic 3D structures. Talk about bending over backwards to escape a situation.
The researchers explain that Kcnq1ot1 RNA is a paternally expressed lncRNA that represses expression of a large domain containing 14 genes. At least one of those genes, called Kcnq1, escapes from this imprinted silencing in certain tissues during particular times in development. The escape is strong—Kcnq1 RNA levels increase eightfold—much more than just double, as would be expected if the gene simply went from monoallelic to normal biallelic expression levels. The scientists wondered how this happens.
The team found that this escape didn’t have anything to do with methylation—the obvious first suspect. But when they looked at the 3D structure of the chromatin with chromosome conformation capture technology, they saw something pretty cool—tissue-specific and stage-specific chromatin loops formed between the Kcnq1 promoter and new enhancers that the team discovered. And these 3D interactions correlated with the monoallelic-to-biallelic transition. It looks like the enhancers can help genes escape from silencing due to imprinting.
If you get a chance to break away from holiday dinner table, can catch up on the data at Epigenetics and Chromatin, November 2011.