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Molecular and Cellular Biology, June 2007, p. 4058-4069, Vol. 27, No. 11
0270-7306/07/$08.00+0 doi:10.1128/MCB.02044-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Howard Hughes Medical Institute, Department of Oncological Sciences, Huntsman Cancer Institute, 2000 Circle of Hope, University of Utah, Salt Lake City, Utah 84112,1 The Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, United Kingdom,2 Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 100213
Received 1 November 2006/ Returned for modification 19 December 2006/ Accepted 9 March 2007
In this study, we characterize a four-protein nucleosome-binding complex from Schizosaccharomyces pombe, termed SAPHIRE, that includes two orthologs of human Lsd1, a histone demethylase. The SAPHIRE complex is essential for cell viability, whereas saphire mutants lacking key conserved catalytic residues are viable but thermosensitive, suggesting that SAPHIRE has both an important enzymatic function and an essential nonenzymatic function. SAPHIRE is present in (or adjacent to) particular heterochromatic loci and also in the transcription start site regions of many highly active polymerase II genes. However, ribosomal protein genes are notably SAPHIRE deficient. SAPHIRE promotes activation, as target genes are selectively attenuated in saphire mutants. Interestingly, saphire mutants display increased histone H3 lysine 4 dimethylation, a modification typically associated with euchromatin. SAPHIRE localization is dynamic, as activated genes rapidly acquire SAPHIRE. Furthermore, saphire mutants dramatically shift a heterochromatin-euchromatin boundary in Chr1, suggesting a novel role in boundary regulation.
Published ahead of print on 19 March 2007.
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