Deletions of three yeast genes, SET2, CDC73, and DST1, involved in 
transcriptional elongation and/or chromatin metabolism were used in conjunction 
with genetic array technology to screen approximately 4700 yeast deletions and 
identify double deletion mutants that produce synthetic growth defects. Of the 
five deletions interacting genetically with all three starting mutations, one 
encoded the histone H2A variant Htz1 and three encoded components of a novel 13 
protein complex, SWR-C, containing the Snf2 family ATPase, Swr1. The SWR-C also 
copurified with Htz1 and Bdf1, a TFIID-interacting protein that recognizes 
acetylated histone tails. Deletions of the genes encoding Htz1 and seven 
nonessential SWR-C components caused a similar spectrum of synthetic growth 
defects when combined with deletions of 384 genes involved in transcription, 
suggesting that Htz1 and SWR-C belong to the same pathway. We show that 
recruitment of Htz1 to chromatin requires the SWR-C. Moreover, like Htz1 and 
Bdf1, the SWR-C promotes gene expression near silent heterochromatin.