Abstract
The Chromosome Passenger Complex (CPC) generates chromosome autonomous signals that regulate mitotic events critical for genome stability. Tip60 is a lysine acetyltransferase that is a tumor suppressor and is targeted for proteasomal degradation by oncogenic papilloma viruses. Mitotic regulation requires the localization of the CPC to inner centromeres, which is driven by the Haspin kinase phosphorylating histone H3 on threonine 3 (H3T3ph). Here we describe how Tip60 acetylates histone H3 at lysine 4 (H3K4ac) to block both the H3T3ph writer and the reader to ensure that this mitotic signaling cannot begin before prophase. Specifically, H3K4ac inhibits Haspin phosphorylation of H3T3 and prevents binding of the Survivin subunit to H3T3ph. Tip60 acetylates H3K4 during S/G2 at centromeres. Inhibition of Tip60 allows the CPC to bind centromeres in G2 cells, and targeting of Tip60 to centromeres prevents CPC localization in mitosis. The H3K4ac mark is removed in prophase by HDAC3 to initiate the CPC localization cascade. Together, our results suggest that Tip60 and HDAC3 temporally control H3K4 acetylation to precisely time the targeting of the CPC to inner centromeres.
Original language | English (US) |
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Article number | br15 |
Journal | Molecular biology of the cell |
Volume | 33 |
Issue number | 9 |
DOIs | |
State | Published - Aug 1 2022 |
Funding
The work described here was supported by NIH Grants No. GM118798 and No. GM124042 to P.T.S., No. GM126900 to B.D.S., No. GM053163 to W.M.; E.N. was supported by a grant from the Schiff foundation. The structural data shown in this report used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. Use of the SBC 19-ID sector was supported by the Structural Biology Center (SBC). Use of the LS-CAT Sector 21 was supported by the Michigan Economic Development Corporation and the Michigan Technology Tri-Corridor (Grant No. 085P1000817).
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
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Dive into the research topics of 'Tip60 acetylation of histone H3K4 temporally controls chromosome passenger complex localization'. Together they form a unique fingerprint.Datasets
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Crystal structure of human Survivin bound to histone H3 T3phK4me1 peptide
Niedzialkowska, E. (Contributor), Liu, L. (Contributor), Kuscu, C. (Contributor), Mayo, Z. (Contributor), Minor, W. (Contributor), Strahl, B. D. (Contributor), Adli, M. (Contributor) & Stukenberg, P. T. (Contributor), Protein Data Bank (PDB), Jan 12 2022
DOI: 10.2210/pdb7LBO/pdb, https://www.wwpdb.org/pdb?id=pdb_00007lbo
Dataset
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Crystal structure of human Survivin bound to histone H3T3phK4ac peptide
Niedzialkowska, E. (Contributor), Liu, L. (Contributor), Kuscu, C. (Contributor), Mayo, Z. (Contributor), Minor, W. (Contributor), Strahl, B. D. (Contributor), Adli, M. (Contributor) & Stukenberg, P. T. (Contributor), Protein Data Bank (PDB), Jan 12 2022
DOI: 10.2210/pdb7LBP/pdb, https://www.wwpdb.org/pdb?id=pdb_00007lbp
Dataset
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Crystal structure of human Survivin bound to histone H3 T3phK4me3 peptide
Niedzialkowska, E. (Contributor), Liu, L. (Contributor), Kuscu, C. (Contributor), Mayo, Z. (Contributor), Minor, W. (Contributor), Strahl, B. D. (Contributor), Adli, M. (Contributor) & Stukenberg, P. T. (Contributor), Protein Data Bank (PDB), Jan 12 2022
DOI: 10.2210/pdb7LBK/pdb, https://www.wwpdb.org/pdb?id=pdb_00007lbk
Dataset