Chromatin can be modified by posttranslational modifications of histones, 
ATP-dependent remodeling, and incorporation of histone variants. The 
Saccharomyces cerevisiae protein Yaf9 is a subunit of both the essential histone 
acetyltransferase complex NuA4 and the ATP-dependent chromatin remodeling 
complex SWR1-C, which deposits histone variant H2A.Z into euchromatin. Yaf9 
contains a YEATS domain, found in proteins associated with multiple 
chromatin-modifying enzymes and transcription complexes across eukaryotes. Here, 
we established the conservation of YEATS domain function from yeast to human, 
and determined the structure of this region from Yaf9 by x-ray crystallography 
to 2.3 A resolution. The Yaf9 YEATS domain consisted of a beta-sandwich 
characteristic of the Ig fold and contained three distinct conserved structural 
features. The structure of the Yaf9 YEATS domain was highly similar to that of 
the histone chaperone Asf1, a similarity that extended to an ability of Yaf9 to 
bind histones H3 and H4 in vitro. Using structure-function analysis, we found 
that the YEATS domain was required for Yaf9 function, histone variant H2A.Z 
chromatin deposition at specific promoters, and H2A.Z acetylation.