While all cells in the body share the same genetic material in DNA, different cell types can turn different genes on or off by controlling the access to DNA. DNA is wound up like a spool with proteins in a complex called chromatin. Stem cells can choose and commit to different cell fates by carefully rearranging the organization of chromatin. Our research has shown that a new class of genes called long noncoding RNAs appear to have an important role in telling which genes stay on. This occurs by the RNAs talking to proteins that keep chromatin in an active configuration. We have also developed new methods to measure the location of open chromatin sites much more rapidly and sensitively than previously possible.
Many long noncoding RNAs emanate from active gene switches called enhancers. We found that one noncoding RNA named 7SK is needed to limit the production of enhancer RNAs, especially in human and mouse embryonic stem cells. The 7SK brake is needed to prevent excess enhancer RNA production that damages the enhancer DNA. Thus, we discovered a system that ensures genome integrity in embryonic stem cells and likely other cell types.