Variant histone H2AZ-containing nucleosomes are involved in the regulation of 
gene expression. In Saccharomyces cerevisiae, chromatin deposition of histone 
H2AZ is mediated by the fourteen-subunit SWR1 complex, which catalyzes 
ATP-dependent exchange of nucleosomal histone H2A for H2AZ. Previous work 
defined the role of seven SWR1 subunits (Swr1 ATPase, Swc2, Swc3, Arp6, Swc5, 
Yaf9, and Swc6) in maintaining complex integrity and H2AZ histone replacement 
activity. Here we examined the function of three additional SWR1 subunits, 
bromodomain containing Bdf1, actin-related protein Arp4 and Swc7, by analyzing 
affinity-purified mutant SWR1 complexes. We observed that depletion of Arp4 
(arp4-td) substantially impaired the association of Bdf1, Yaf9, and Swc4. In 
contrast, loss of either Bdf1 or Swc7 had minimal effects on overall complex 
integrity. Furthermore, the basic H2AZ histone replacement activity of SWR1 in 
vitro required Arp4, but not Bdf1 or Swc7. Thus, three out of fourteen SWR1 
subunits, Bdf1, Swc7, and previously noted Swc3, appear to have roles auxiliary 
to the basic histone replacement activity. The N-terminal region of the Swr1 
ATPase subunit is necessary and sufficient to direct association of Bdf1 and 
Swc7, as well as Arp4, Act1, Yaf9 and Swc4. This same region contains an 
additional H2AZ-H2B specific binding site, distinct from the previously 
identified Swc2 subunit. These findings suggest that one SWR1 enzyme might be 
capable of binding two H2AZ-H2B dimers, and provide further insight on the 
hierarchy and interdependency of molecular interactions within the SWR1 complex.