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Molecular and Cellular Biology, January 2005, p. 590-601, Vol. 25, No. 2
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.2.590-601.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Global Effects on Gene Expression in Fission Yeast by Silencing and RNA Interference Machineries{dagger}

Klavs R. Hansen,1 Gavin Burns,2 Juan Mata,2 Thomas A. Volpe,3 Robert A. Martienssen,3 Jürg Bähler,2 and Geneviève Thon1*

Department of Genetics, Institute of Molecular Biology, University of Copenhagen, Copenhagen, Denmark,1 The Wellcome Trust Sanger Institute, Cambridge, United Kingdom,2 Cold Spring Harbor Laboratory, Cold Spring Harbor, New York3

Received 27 April 2004/ Returned for modification 28 June 2004/ Accepted 13 September 2004

Histone modifications influence gene expression in complex ways. The RNA interference (RNAi) machinery can repress transcription by recruiting histone-modifying enzymes to chromatin, although it is not clear whether this is a general mechanism for gene silencing or whether it requires repeated sequences such as long terminal repeats (LTRs). We analyzed the global effects of the Clr3 and Clr6 histone deacetylases, the Clr4 methyltransferase, the zinc finger protein Clr1, and the RNAi proteins Dicer, RdRP, and Argonaute on the transcriptome of Schizosaccharomyces pombe (fission yeast). The clr mutants derepressed similar subsets of genes, many of which also became transcriptionally activated in cells that were exposed to environmental stresses such as nitrogen starvation. Many genes that were repressed by the Clr proteins clustered in extended regions close to the telomeres. Surprisingly few genes were repressed by both the silencing and RNAi machineries, with transcripts from centromeric repeats and Tf2 retrotransposons being notable exceptions. We found no correlation between repression by RNAi and proximity to LTRs, and the wtf family of repeated sequences seems to be repressed by histone deacetylation independent of RNAi. Our data indicate that the RNAi and Clr proteins show only a limited functional overlap and that the Clr proteins play more global roles in gene silencing.

* Corresponding author. Mailing address: Department of Genetics, Institute of Molecular Biology, University of Copenhagen, Øster Farimagsgade 2A, Copenhagen 1353 K, Denmark. Phone: 45-3532-2108. Fax: 45-3532-2113. E-mail: gen{at}biobase.dk.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, January 2005, p. 590-601, Vol. 25, No. 2
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.2.590-601.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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