Histone mark recognition controls nucleosome translocation via a kinetic proofreading mechanism: Confronting theory and high-throughput experiments

Chromatin remodelers are multidomain enzymatic motor complexes that displace nucleosomes along DNA and hence “remodel chromatin structure,” i.e., they dynamically reorganize nucleosome positions in both gene activation and gene repression. Recently, experimental insights from structural biology methods and remodeling assays have substantially advanced the understanding of these key chromatin components. Here we confront the kinetic proofreading scenario of chromatin remodeling, which proposes a mechanical link between histone residue modifications and the ATP-dependent action of remodelers, with recent experiments. We show that recent high-throughput data on nucleosome libraries assayed with remodelers from the Imitation Switch family are in accord with our earlier predictions of the kinetic proofreading scenario. We make suggestions for experimentally verifiable predictions of the kinetic proofreading scenarios for remodelers from other families.

Figure 1

Kinetic proofreading scheme for chromatin remodeling with nucleosome ($N$), remodeler ($R$), complex ($I$), activated complex ($I^{*}$), and mobile nucleosome ($M$). The translocation step with rate $p$ is shown to lead to remodeler dissociation; it should be noted that this step is in general processive.