Genomewide dynamics of SAPHIRE: a novel histone demethylase comples

We have isolated a novel four-protein complex from S. pombe termed SAPHIRE that bears two proteins similar to human LSDl, a known histone demethylase/amine oxidase, and two proteins with PHD domains, a motif that interacts with histones. SAPHIRE binds nucleosomes with high affinity, but lacks detectable in vitro demethylase activity under the conditions tested. Genetic experiments reveal that SAPHIRE is essential for cell viability. Interestingly, strains bearing hypomorphic alleles designed to eliminate amine oxidase activity grow well, but exhibit thermosensitivity, suggesting that SAPHIRE bears both an important catalytic activity and an essential nonenzymatic function. Genomewide localization reveals that SAPHIRE occupies at least three distinct classes of targets in vivo: Pol II promoters, kinetochores and chromatin domain boundaries. The class that includes the largest number of targets is Pol II promoters. SAPHIRE localizes near the transcription start site of a significant fraction of highly active Pol II genes, although SAPHIRE is notably absent at ribosomal protein genes. SAPHIRE promotes gene activation, as SAPHIRE-occupied genes are selectively attenuated in SAPHIRE mutants.