For the first time, the molecular machines known as “chromatin remodelers” have been found to spend much of their time rapidly searching for their nucleosome soulmates. And, just like desperate singles at a Speed Dating party, they keep at it until they find the right one.
Chromatin remodelers help organize the genome, control DNA accessibility, and can move nucleosomes along the DNA chain to establish their patterns on newly synthesized DNA during cell division, or switch between “on” and “off” gene expression states.
Through experiments with live cells, Karsten Rippe at the DKFZ in Heidelberg, Gernot Längst at the University of Regensburg, and their teams discovered that roughly one million remodeler complexes exist in a single human cell nucleus, and that they move surprisingly fast. So, how do they find the “right” nucleosome? A given remodeler binds to a nucleosome for only about 1/10th to 1/100th of a second, and then detaches to test another until it finds the perfect one that binds it tightly. If the two fit together well, the remodeler hooks up to the nucleosome: staying for seconds or even minutes to shift it to a new position on the DNA, before it dissociates. In special cases, like when DNA is damaged and needs repaired, many nucleosomes are repositioned and remodelers will accumulate at this “activity hotspot”. Because there are so many remodelers, and they are always searching for matches, it takes them only a few seconds to recognize the DNA damage signals and spring into action. As lead author Fabian Erdel from DKFZ puts it: “Remodelers come and go and you can hardly keep them in place. But if you need them they show up in no time”.
The misinterpretation of epigenetic nucleosome signals due to aberrant chromatin remodeler activity is linked to several types of cancers, so the next challenge will be to decipher how different signals that make remodelers stick to one nucleosome but not others.
Get a front row seat to the chromatin remodeler search for the perfect nucleosome match at Proceedings of the National Academy of Sciences, October 2010.