An Rtt109-independent role for Vps75 in transcription-associated nucleosome dynamics

Date

2009

Authors

Selth, L.
Lorch, Y.
Ocampo-Hafalla, M.
Mitter, R.
Shales, M.
Krogan, N.
Kornberg, R.
Svejstrup, J.

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Journal article

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Molecular and Cellular Biology, 2009; 29(15):4220-4234

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Luke A. Selth, Yahli Lorch, Maria T. Ocampo-Hafalla, Richard Mitter, Michael Shales, Nevan J. Krogan, Roger D. Kornberg, and Jesper Q. Svejstrup

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Abstract

The histone chaperone Vps75 forms a complex with, and stimulates the activity of, the histone acetyltransferase Rtt109. However, Vps75 can also be isolated on its own and might therefore possess Rtt109-independent functions. Analysis of epistatic miniarray profiles showed that VPS75 genetically interacts with factors involved in transcription regulation whereas RTT109 clusters with genes linked to DNA replication/repair. Additional genetic and biochemical experiments revealed a close relationship between Vps75 and RNA polymerase II. Furthermore, Vps75 is recruited to activated genes in an Rtt109-independent manner, and its genome-wide association with genes correlates with transcription rate. Expression microarray analysis identified a number of genes whose normal expression depends on VPS75. Interestingly, histone H2B dynamics at some of these genes are consistent with a role for Vps75 in histone H2A/H2B eviction/deposition during transcription. Indeed, reconstitution of nucleosome disassembly using the ATP-dependent chromatin remodeler Rsc and Vps75 revealed that these proteins can cooperate to remove H2A/H2B dimers from nucleosomes. These results indicate a role for Vps75 in nucleosome dynamics during transcription, and importantly, this function appears to be largely independent of Rtt109.

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Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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