ATP-Driven Exchange of Histone H2AZ Variant Catalyzed by SWR1 Chromatin Remodeling Complex

TLDR

The histone variant H2AZ regulates gene expression and buffers silent heterochromatin, yet how it is incorporated into nucleosomes remains unclear. The Swi2/Snf2 ATPase Swr1 acts as the catalytic core of a multisubunit exchanger that efficiently replaces H2A with H2AZ in nucleosomes, is required for H2AZ deposition at specific chromosomal sites, and together with H2AZ regulates a subset of yeast genes, revealing a novel role for ATP‑dependent chromatin remodeling.

Abstract

The conserved histone variant H2AZ has an important role in the regulation of gene expression and the establishment of a buffer to the spread of silent heterochromatin. How histone variants such as H2AZ are incorporated into nucleosomes has been obscure. We have found that Swr1, a Swi2/Snf2-related adenosine triphosphatase, is the catalytic core of a multisubunit, histone-variant exchanger that efficiently replaces conventional histone H2A with histone H2AZ in nucleosome arrays. Swr1 is required for the deposition of histone H2AZ at specific chromosome locations in vivo, and Swr1 and H2AZ commonly regulate a subset of yeast genes. These findings define a previously unknown role for the adenosine triphosphate-dependent chromatin remodeling machinery.