A Snf2 Family ATPase Complex Required for Recruitment of the Histone H2A Variant Htz1

Abstract

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.

Expanding the Functional Repertoire of CTD Kinase I and RNA Polymerase II: Novel PhosphoCTD-Associating Proteins in the Yeast Proteome

“…However, this situation may be largely explained by our very incomplete knowledge of both the multifunctional nature of proteins in general (111)(112)(113) and the functional organization of the nucleus in particular. That the observed physical interactions likely do have functional significance in vivo is implied by the number of genetic interactions between or among PCAPs and associated proteins [SGD (58,71,72) and Table 2 of Supporting Information]. These genetic interactions are reminiscent of those typifying Ctk1 and the subset of PCAPs described earlier: Set2, Ssd1, and Hrr25.…”

“…Similar profiles were observed for almost all such complexes as described in either ref 70 or ref 69 (see Table 1 of Supporting Information and Discussion). Intriguingly, in addition to such physical interactions, these proteins also interact with each other genetically [SGD, Saccharomyces Genome Database, http://www.yeastgenome.org/ (58,71,72)], indicating that the observed physical interactions also have functional significance in vivo (Table 2 of Supporting Information). In addition, several of the proteins have been found to interact genetically with genes encoding transcription elongation-related functions, such as CDC73 (58,71,72).…”

“…Intriguingly, in addition to such physical interactions, these proteins also interact with each other genetically [SGD, Saccharomyces Genome Database, http://www.yeastgenome.org/ (58,71,72)], indicating that the observed physical interactions also have functional significance in vivo (Table 2 of Supporting Information). In addition, several of the proteins have been found to interact genetically with genes encoding transcription elongation-related functions, such as CDC73 (58,71,72). Moreover, such genes encoding transcription elongation-related functions (e.g., CDC73) in their turn interact genetically with CTK1 (71)(72)(73).…”

Mechanisms of ATP dependent chromatin remodeling

“…Almost at the same time three groups discovered the existence of this ∼13 subunit complex that interacts with the histone variant H2A.Z [115][116][117]. The catalytic subunit of this complex is Swr1 which has an ATPase domain related to Snf2.…”

INO80 subfamily of chromatin remodeling complexes

“…The SWR1 complex was found to be able to specifically exchange histone H2A in nucleosomes for its variant H2AZ by three laboratories using different experimental approaches [9,62,63]. The purified yeast SWR1 complex contains fourteen polypeptides: Swr1, Swc2/Vp372, Swc3, Swc4/Eaf2/God1, Swc5/Aor1, Swc6/Vps71, Swc7, Yaf9, Bdf1, Act1/actin, Arp4, Arp6, Rvb1 and Rvb2 (Figure 1) [9,64].…”