Survivin prevents the polycomb repressor complex 2 from methylating histone 3 lysine 27
Maja Jensen,
Venkataragavan Chandrasekaran,
María-José García-Bonete,
Shuxiang Li,
Atsarina Larasati Anindya,
Karin Andersson,
Malin C. Erlandsson,
Nina Y. Oparina,
Björn M. Burmann,
Ulrika Brath,
Anna R. Panchenko,
Maria Bokarewa I.,
Gergely Katona
Affiliations
Maja Jensen
Department of Chemistry and Molecular Biology, Faculty of Science, University of Gothenburg, Box 462, 405 30 Gothenburg, Sweden
Venkataragavan Chandrasekaran
Department of Rheumatology and Inflammation Research, Institute of Medicine, University of Gothenburg, Box 480, 40530 Gothenburg, Sweden
María-José García-Bonete
Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Box 440, 405 30 Gothenburg, Sweden
Shuxiang Li
Department of Pathology and Molecular Medicine, School of Medicine, Queen’s University, Kingston, ON K7L 3N6, Canada
Atsarina Larasati Anindya
Department of Chemistry and Molecular Biology, Faculty of Science, University of Gothenburg, Box 462, 405 30 Gothenburg, Sweden
Karin Andersson
Department of Rheumatology and Inflammation Research, Institute of Medicine, University of Gothenburg, Box 480, 40530 Gothenburg, Sweden
Malin C. Erlandsson
Department of Rheumatology and Inflammation Research, Institute of Medicine, University of Gothenburg, Box 480, 40530 Gothenburg, Sweden
Nina Y. Oparina
Department of Rheumatology and Inflammation Research, Institute of Medicine, University of Gothenburg, Box 480, 40530 Gothenburg, Sweden
Björn M. Burmann
Department of Chemistry and Molecular Biology, Faculty of Science, University of Gothenburg, Box 462, 405 30 Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, 405 30 Gothenburg, Sweden
Ulrika Brath
Department of Chemistry and Molecular Biology and the Swedish NMR Centre, University of Gothenburg, 412 96 Gothenburg, Sweden
Anna R. Panchenko
Department of Pathology and Molecular Medicine, School of Medicine, Queen’s University, Kingston, ON K7L 3N6, Canada
Maria Bokarewa I.
Department of Rheumatology and Inflammation Research, Institute of Medicine, University of Gothenburg, Box 480, 40530 Gothenburg, Sweden; Rheumatology Clinic, Sahlgrenska University Hospital, Gröna stråket 16, 41346 Gothenburg, Sweden
Gergely Katona
Department of Chemistry and Molecular Biology, Faculty of Science, University of Gothenburg, Box 462, 405 30 Gothenburg, Sweden; Corresponding author
Summary: This study investigates the role of survivin in epigenetic control of gene transcription through interaction with the polycomb repressive complex 2 (PRC2). PRC2 is responsible for silencing gene expression by trimethylating lysine 27 on histone 3. We observed differential expression of PRC2 subunits in CD4+ T cells with varying levels of survivin expression, and ChIP-seq results indicated that survivin colocalizes with PRC2 along DNA. Inhibition of survivin resulted in a significant increase in H3K27 trimethylation, implying that survivin prevents PRC2 from functioning. Peptide microarray showed that survivin interacts with peptides from PRC2 subunits, and machine learning revealed that amino acid composition contains relevant information for predicting survivin interaction. NMR and BLI experiments supported the interaction of survivin with PRC2 subunit EZH2. Finally, protein-protein docking revealed that the survivin-EZH2 interaction interface overlaps with catalytic residues of EZH2, potentially inhibiting its H3K27 methylation activity. These findings suggest that survivin inhibits PRC2 function.
