Fission yeast homologs of human histone H3 lysine 4 demethylase regulate a common set of genes with diverse functions.
Schizosaccharomyces pombe contains two proteins, SWIRM1 and SWIRM2, with close homology to human histone H3 lysine 4 demethylase. Both proteins contain the amino oxidase catalytic domain and a recently described DNA interaction SWIRM domain. Here we describe the biochemical isolation and the functional characterization of SWIRM1 and SWIRM2. Our results indicate that while SWIRM2 is an essential gene, cells lacking SWIRM1 are viable. We found that SWIRM1 and SWIRM2 are stably associated in a multiprotein complex, but intriguingly, unlike their human counterpart, S. pombe SWIRM complex contains neither a histone deacetylase nor any detectable demethylase activity. Genome-wide chromatin immunoprecipitation unexpectedly showed the absence of both SWIRM proteins from heterochromatic domains. Instead, consistent with biochemical analyses, SWIRM1 and SWIRM2 co-localize to a common set of target gene promoters whose functions are implicated in diverse processes including mitochondrial metabolism and transcriptional regulation. Importantly, we show that SWIRM1 is not only required for optimum transcription of its target genes but also display a global role in regulation of antisense transcription.
Nicolas
Estelle
E
Laboratory of Molecular Cell Biology, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA.
Lee
Min Gyu
MG
Hakimi
Mohamed-Ali
MA
Cam
Hugh P
HP
Grewal
Shiv I S
SI
Shiekhattar
Ramin
R
D002843:Chromatin / Q000737:chemistry; D047369:Chromatin Immunoprecipitation; D017353:Gene Deletion; D016678:Genome; D016681:Genome, Fungal; D011495:Histone-Lysine N-Methyltransferase / Q000737:chemistry*; D006657:Histones / Q000737:chemistry; D006801:Humans; D008957:Models, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012568:Schizosaccharomyces / Q000201:enzymology* / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry; D014158:Transcription, Genetic
D002843:Chromatin; D006657:Histones; D029702:Schizosaccharomyces pombe Proteins; D011495:Histone-Lysine N-Methyltransferase