A proposal for kinetic proof reading by ISWI family chromatin remodeling motors

Abstract

ATP-dependent chromatin remodeling motors play fundamental roles in nuclear processes by regulating access to DNA. Yet compared to other cellular motors less is known about how these motors couple the energy of ATP to alter their substrates. Here we use recent studies on a key chromatin remodeling motor from the ISWI class, human ACF and its yeast counterpart, ISW2, to propose a model for how these motors use ATP to read structural cues presented by nucleosomal substrates. Substantial earlier work has shown that ACF activity is strongly regulated by the length of the DNA flanking a nucleosome as well as by the histone H4 tail. Recent bulk and single-molecule studies of human ACF suggest that this complex functions as a dimeric motor. These studies, together with studies of yeast ISW2 imply that at least two types of ATP hydrolysis events accompany each cycle of nucleosome movement. We propose that ISWI motors may employ a kinetic proof reading type of mechanism to favor action on nucleosomes that are poised to be in condensed chromatin while inhibiting action on nucleosomes that are in fully active or fully condensed chromatin.