The Set1/COMPASS histone H3 methyltransferase helps regulate mitosis with the CDK1 and NIMA mitotic kinases in Aspergillus nidulans.
Mitosis is promoted and regulated by reversible protein phosphorylation catalyzed by the essential NIMA and CDK1 kinases in the model filamentous fungus Aspergillus nidulans. Protein methylation mediated by the Set1/COMPASS methyltransferase complex has also been shown to regulate mitosis in budding yeast with the Aurora mitotic kinase. We uncover a genetic interaction between An-swd1, which encodes a subunit of the Set1 protein methyltransferase complex, with NIMA as partial inactivation of nimA is poorly tolerated in the absence of swd1. This genetic interaction is additionally seen without the Set1 methyltransferase catalytic subunit. Importantly partial inactivation of NIMT, a mitotic activator of the CDK1 kinase, also causes lethality in the absence of Set1 function, revealing a functional relationship between the Set1 complex and two pivotal mitotic kinases. The main target for Set1-mediated methylation is histone H3K4. Mutational analysis of histone H3 revealed that modifying the H3K4 target residue of Set1 methyltransferase activity phenocopied the lethality seen when either NIMA or CDK1 are partially functional. We probed the mechanistic basis of these genetic interactions and find that the Set1 complex performs functions with CDK1 for initiating mitosis and with NIMA during progression through mitosis. The studies uncover a joint requirement for the Set1 methyltransferase complex with the CDK1 and NIMA kinases for successful mitosis. The findings extend the roles of the Set1 complex to include the initiation of mitosis with CDK1 and mitotic progression with NIMA in addition to its previously identified interactions with Aurora and type 1 phosphatase in budding yeast.
Department of Molecular Genetics, The Ohio State University, Columbus, Ohio 43220 Molecular, Cellular, and Developmental Biology Program, The Ohio State University, Columbus, Ohio 43220.
Meera
M
Govindaraghavan
Department of Biology, Millsaps College, Jackson, Mississippi 39210.
Sarah Lea
SL
Anglin
Department of Molecular Genetics, The Ohio State University, Columbus, Ohio 43220 Molecular, Cellular, and Developmental Biology Program, The Ohio State University, Columbus, Ohio 43220 Department of Biology, Millsaps College, Jackson, Mississippi 39210.
Aysha H
AH
Osmani
Department of Molecular Genetics, The Ohio State University, Columbus, Ohio 43220 Molecular, Cellular, and Developmental Biology Program, The Ohio State University, Columbus, Ohio 43220 osmani.2@osu.edu.
Stephen A
SA
Osmani
D001233:Aspergillus nidulans / Q000166:cytology* / Q000235:genetics; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D008938:Mitosis / Q000235:genetics; D000072380:NIMA-Related Kinase 1; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D006657:Histones; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D000072380:NIMA-Related Kinase 1; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase
CDK1; NIMA; Set1; histone H3K4; mitosis