Chromatin Remodelers

Active Brownian Dimers and Kinetic Proofreading

Chromatin remodelers are multidomain enzymatic motor complexes that displace nucleosomes along DNA. A recent experimental breakthrough based on cryo-EM allows now to understand how (some of the) remodellers work at the microscopic level. Remodelers use the intrinsic mobility of nucleosomes that is based on twist defects in the wrapped DNA, as described by us earlier (Kulic 2003). They can be best understood as active Brownian dimers (Blossey 2019a) that – as they walk along the nucleosomal DNA – create pairs of over- and under-twist defects, see (Schiessel 2019) for a detailed commentary.

Typical structure and action of a chromatin remodeler — Two representations of the action of a chromatin remodeler on nucleosomal DNA: side-view of the engagement of the two remodeler lobes with the two turns of DNA (left) and mapping of the remodeler-DNA contacts on the two remodeler footprints denoted by coordinates along the DNA (right) (Blossey 2019a).

How do remodelers know on which nucleosomes they should act? In 2008 we put forward a kinetic proofreading scheme that might explain how an ATP-consumption step of the remodeler allows it to target specific nucleosomes (Blossey 2008). Recent high-throughput data on nucleosome libraries assayed with remodelers are in accord with our earlier prediction of a kinetic proofreading scenario (Blossey 2019b).

Kinetic proofreading scheme for chromatin remodeling with nucleosome (N), remodeler (R), complex (I), activated complex (I∗), and mobile nucleosome (M) (Blossey 2019b).