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Structure of the Human Core Centromeric Nucleosome Complex.

Allu PK, Dawicki-McKenna JM, Van Eeuwen T, Slavin M, Braitbard M, Xu C, Kalisman N, Murakami K, Black BE
Curr Biol 29 2625-2639.e5 (2019)
Cited: 32 times
EuropePMC logo PMID: 31353180

Abstract

Centromeric nucleosomes are at the interface of the chromosome and the kinetochore that connects to spindle microtubules in mitosis. The core centromeric nucleosome complex (CCNC) harbors the histone H3 variant, CENP-A, and its binding proteins, CENP-C (through its central domain; CD) and CENP-N (through its N-terminal domain; NT). CENP-C can engage nucleosomes through two domains: the CD and the CENP-C motif (CM). CENP-CCD is part of the CCNC by virtue of its high specificity for CENP-A nucleosomes and ability to stabilize CENP-A at the centromere. CENP-CCM is thought to engage a neighboring nucleosome, either one containing conventional H3 or CENP-A, and a crystal structure of a nucleosome complex containing two copies of CENP-CCM was reported. Recent structures containing a single copy of CENP-NNT bound to the CENP-A nucleosome in the absence of CENP-C were reported. Here, we find that one copy of CENP-N is lost for every two copies of CENP-C on centromeric chromatin just prior to kinetochore formation. We present the structures of symmetric and asymmetric forms of the CCNC that vary in CENP-N stoichiometry. Our structures explain how the central domain of CENP-C achieves its high specificity for CENP-A nucleosomes and how CENP-C and CENP-N sandwich the histone H4 tail. The natural centromeric DNA path in our structures corresponds to symmetric surfaces for CCNC assembly, deviating from what is observed in prior structures using artificial sequences. At mitosis, we propose that CCNC asymmetry accommodates its asymmetric connections at the chromosome/kinetochore interface. VIDEO ABSTRACT.

Articles - 6muo mentioned but not cited (3)

  1. Structure of the Human Core Centromeric Nucleosome Complex. Allu PK, Dawicki-McKenna JM, Van Eeuwen T, Slavin M, Braitbard M, Xu C, Kalisman N, Murakami K, Black BE. Curr Biol 29 2625-2639.e5 (2019)
  2. Cryo-EM structure of the CENP-A nucleosome in complex with phosphorylated CENP-C. Ariyoshi M, Makino F, Watanabe R, Nakagawa R, Kato T, Namba K, Arimura Y, Fujita R, Kurumizaka H, Okumura EI, Hara M, Fukagawa T. EMBO J 40 e105671 (2021)
  3. The cryo-EM structure of the CENP-A nucleosome in complex with ggKNL2. Jiang H, Ariyoshi M, Hori T, Watanabe R, Makino F, Namba K, Fukagawa T. EMBO J 42 e111965 (2023)


Reviews citing this publication (9)

  1. Principles of nucleosome recognition by chromatin factors and enzymes. McGinty RK, Tan S. Curr Opin Struct Biol 71 16-26 (2021)
  2. The centromere comes into focus: from CENP-A nucleosomes to kinetochore connections with the spindle. Kixmoeller K, Allu PK, Black BE. Open Biol 10 200051 (2020)
  3. Guarding the Genome: CENP-A-Chromatin in Health and Cancer. Mahlke MA, Nechemia-Arbely Y. Genes (Basel) 11 E810 (2020)
  4. The Four Causes: The Functional Architecture of Centromeres and Kinetochores. McAinsh AD, Marston AL. Annu Rev Genet 56 279-314 (2022)
  5. CENP-A nucleosome-a chromatin-embedded pedestal for the centromere: lessons learned from structural biology. Ali-Ahmad A, Sekulić N. Essays Biochem 64 205-221 (2020)
  6. Cell-cycle phospho-regulation of the kinetochore. Klemm C, Thorpe PH, Ólafsson G. Curr Genet 67 177-193 (2021)
  7. CENP-A Regulation and Cancer. Renaud-Pageot C, Quivy JP, Lochhead M, Almouzni G. Front Cell Dev Biol 10 907120 (2022)
  8. Meiotic CENP-C is a shepherd: bridging the space between the centromere and the kinetochore in time and space. Fellmeth JE, McKim KS. Essays Biochem 64 251-261 (2020)
  9. Centromere Chromatin Dynamics at a Glance. Shukla S, Kumar A. Epigenomes 6 39 (2022)

Articles citing this publication (20)

  1. CENP-C unwraps the human CENP-A nucleosome through the H2A C-terminal tail. Ali-Ahmad A, Bilokapić S, Schäfer IB, Halić M, Sekulić N. EMBO Rep 20 e48913 (2019)
  2. Structure of the human inner kinetochore bound to a centromeric CENP-A nucleosome. Yatskevich S, Muir KW, Bellini D, Zhang Z, Yang J, Tischer T, Predin M, Dendooven T, McLaughlin SH, Barford D. Science 376 844-852 (2022)
  3. Parallel pathways for recruiting effector proteins determine centromere drive and suppression. Kumon T, Ma J, Akins RB, Stefanik D, Nordgren CE, Kim J, Levine MT, Lampson MA. Cell 184 4904-4918.e11 (2021)
  4. Intrinsic elasticity of nucleosomes is encoded by histone variants and calibrated by their binding partners. Melters DP, Pitman M, Rakshit T, Dimitriadis EK, Bui M, Papoian GA, Dalal Y. Proc Natl Acad Sci U S A 116 24066-24074 (2019)
  5. Structure of the human inner kinetochore CCAN complex and its significance for human centromere organization. Pesenti ME, Raisch T, Conti D, Walstein K, Hoffmann I, Vogt D, Prumbaum D, Vetter IR, Raunser S, Musacchio A. Mol Cell 82 2113-2131.e8 (2022)
  6. Kinetochore assembly throughout the cell cycle. Navarro AP, Cheeseman IM. Semin Cell Dev Biol 117 62-74 (2021)
  7. Assembly principles and stoichiometry of a complete human kinetochore module. Walstein K, Petrovic A, Pan D, Hagemeier B, Vogt D, Vetter IR, Musacchio A. Sci Adv 7 eabg1037 (2021)
  8. CENP-N promotes the compaction of centromeric chromatin. Zhou K, Gebala M, Woods D, Sundararajan K, Edwards G, Krzizike D, Wereszczynski J, Straight AF, Luger K. Nat Struct Mol Biol 29 403-413 (2022)
  9. Stable inheritance of CENP-A chromatin: Inner strength versus dynamic control. Mitra S, Srinivasan B, Jansen LET. J Cell Biol 219 e202005099 (2020)
  10. Structural and dynamic mechanisms of CBF3-guided centromeric nucleosome formation. Guan R, Lian T, Zhou BR, He E, Wu C, Singleton M, Bai Y. Nat Commun 12 1763 (2021)
  11. Structural basis of nucleosomal histone H4 lysine 20 methylation by SET8 methyltransferase. Ho CH, Takizawa Y, Kobayashi W, Arimura Y, Kimura H, Kurumizaka H. Life Sci Alliance 4 e202000919 (2021)
  12. Gene replacement strategies validate the use of functional tags on centromeric chromatin and invalidate an essential role for CENP-AK124ub. Salinas-Luypaert C, Allu PK, Logsdon GA, Dawicki-McKenna JM, Gambogi CW, Fachinetti D, Black BE. Cell Rep 37 109924 (2021)
  13. Human Histone Interaction Networks: An Old Concept, New Trends. Peng Y, Markov Y, Goncearenco A, Landsman D, Panchenko AR. J Mol Biol 433 166684 (2021)
  14. Permitted and restricted steps of human kinetochore assembly in mitotic cell extracts. Tarasovetc EV, Allu PK, Wimbish RT, DeLuca JG, Cheeseman IM, Black BE, Grishchuk EL. Mol Biol Cell 32 1241-1255 (2021)
  15. Dynamic cell cycle-dependent phosphorylation modulates CENP-L-CENP-N centromere recruitment. Navarro AP, Cheeseman IM. Mol Biol Cell 33 ar87 (2022)
  16. ZCMM: A Novel Method Using Z-Curve Theory- Based and Position Weight Matrix for Predicting Nucleosome Positioning. Cui Y, Xu Z, Li J. Genes (Basel) 10 E765 (2019)
  17. Multi-site phosphorylation of yeast Mif2/CENP-C promotes inner kinetochore assembly. Hinshaw SM, Quan Y, Cai J, Zhou AL, Zhou H. Curr Biol 33 688-696.e6 (2023)
  18. CENP-A and CENP-B collaborate to create an open centromeric chromatin state. Nagpal H, Ali-Ahmad A, Hirano Y, Cai W, Halic M, Fukagawa T, Sekulić N, Fierz B. Nat Commun 14 8227 (2023)
  19. Clinical implications and immune features of CENPN in breast cancer. Gui Z, Tian Y, Yu T, Liu S, Liu C, Zhang L. BMC Cancer 23 851 (2023)
  20. On the Regulation of Mitosis by the Kinetochore, a Macromolecular Complex and Organising Hub of Eukaryotic Organisms. Bolanos-Garcia VM. Subcell Biochem 99 235-267 (2022)


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