Genome-wide dynamics of SAPHIRE, an essential complex for gene activation and chromatin boundaries.
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.
Gordon
Matthew
M
University of Utah, Huntsman Cancer Institute, 2000 Circle of Hope, Salt Lake City, UT 84112, USA.
Holt
Derick G
DG
Panigrahi
Anil
A
Wilhelm
Brian T
BT
Erdjument-Bromage
Hediye
H
Tempst
Paul
P
Bähler
Jürg
J
Cairns
Bradley R
BR
D000595:Amino Acid Sequence; D000818:Animals; D002470:Cell Survival; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation; D016681:Genome, Fungal; D018869:Heat-Shock Response; D056466:Histone Demethylases; D006657:Histones / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D009707:Nucleosomes / Q000378:metabolism*; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D016415:Sequence Alignment; D016615:Telomere / Q000378:metabolism; D015533:Transcriptional Activation
D002843:Chromatin; D006657:Histones; D046912:Multiprotein Complexes; D009707:Nucleosomes; D021122:Protein Subunits; D029702:Schizosaccharomyces pombe Proteins; D056466:Histone Demethylases; C495195:KDM1A protein, human; D010089:Oxidoreductases, N-Demethylating