Abstract
The nucleosome is a DNA–protein assembly that is the basic unit of chromatin. A nucleosome can adopt various structures. In the canonical nucleosome structure, 145–147 bp of DNA is wrapped around a histone heterooctamer. The strong histone-DNA interactions cause the DNA to be inaccessible for nuclear processes such as transcription. Therefore, the canonical nucleosome structure has to be altered into different, non-canonical structures to increase DNA accessibility. While it is recognised that non-canonical structures do exist, these structures are not well understood. In this review, we discuss both the evidence for various non-canonical nucleosome structures in the nucleus and the factors that are believed to induce these structures. The wide range of non-canonical structures is likely to regulate the amount of accessible DNA, and thus have important nuclear functions.
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Abbreviations
- Cryo-ET:
-
Electron cryotomography/cryo-electron tomography
References
Ali-Ahmad A, Bilokapic S, Schafer IB, Halic M, Sekulic N (2019) CENP-C unwraps the human CENP-A nucleosome through the H2A C-terminal tail. EMBO Rep 20(10):e48913. https://doi.org/10.15252/embr.20194891
Armache JP, Gamarra N, Johnson SL, Leonard JD, Wu S, Narlikar GJ, & Cheng Y (2019) Cryo-EM structures of remodeler-nucleosome intermediates suggest allosteric control through the nucleosome. Elife, 8 https://doi.org/10.7554/eLife.46057
Armeev GA, Gribkova AK, Pospelova I, Komarova GA, Shaytan AK (2019) Linking chromatin composition and structural dynamics at the nucleosome level. Curr Opin Struct Biol 56:46–55. https://doi.org/10.1016/j.sbi.2018.11.006
Asano, S., Fukuda, Y., Beck, F., Aufderheide, A., Forster, F., Danev, R., & Baumeister, W. (2015). Proteasomes. A molecular census of 26S proteasomes in intact neurons. Science, 347(6220), 439-442. https://doi.org/10.1126/science.1261197
Axel R, Melchior W Jr, Sollner-Webb B, Felsenfeld G (1974) Specific sites of interaction between histones and DNA in chromatin. Proc Natl Acad Sci U S A 71(10):4101–4105. https://doi.org/10.1073/pnas.71.10.4101
Bai Y, Zhou BR (2021) Structures of native-like nucleosomes: one step closer toward understanding the structure and function of chromatin. J Mol Biol 433(6):166648. https://doi.org/10.1016/j.jmb.2020.09.007
Bauerlein FJB, Baumeister W (2021) Towards visual proteomics at high resolution. J Mol Biol 433(20):167187. https://doi.org/10.1016/j.jmb.2021.167187
Bednar J, Garcia-Saez I, Boopathi R, Cutter AR, Papai G, Reymer A, Syed SH, Lone IN, Tonchev O, Crucifix C, Menoni H, Papin C, Skoufias DA, Kurumizaka H, Lavery R, Hamiche A, Hayes JJ, Schultz P, Angelov D, Dimitrov S (2017) Structure and dynamics of a 197 bp nucleosome in complex with linker histone H1. Mol Cell, 66 3, 384–397 e388 https://doi.org/10.1016/j.molcel.2017.04.012
Bepler T, Kelley K, Noble AJ, Berger B (2020) Topaz-Denoise: general deep denoising models for cryoEM and cryoET. Nat Commun 11(1):5208. https://doi.org/10.1038/s41467-020-18952-1
Bharat TA, Russo CJ, Lowe J, Passmore LA, Scheres SH (2015) Advances in single-particle electron cryomicroscopy structure determination applied to sub-tomogram averaging. Structure 23(9):1743–1753. https://doi.org/10.1016/j.str.2015.06.026
Bilokapic S, Strauss M, Halic M (2018) Histone octamer rearranges to adapt to DNA unwrapping. Nat Struct Mol Biol 25(1):101–108. https://doi.org/10.1038/s41594-017-0005-5
Bohm J, Frangakis AS, Hegerl R, Nickell S, Typke D, Baumeister W (2000) Toward detecting and identifying macromolecules in a cellular context: template matching applied to electron tomograms. Proc Natl Acad Sci U S A 97(26):14245–14250. https://doi.org/10.1073/pnas.230282097
Bohning J, Bharat TAM (2021) Towards high-throughput in situ structural biology using electron cryotomography. Prog Biophys Mol Biol 160:97–103. https://doi.org/10.1016/j.pbiomolbio.2020.05.010
Bowerman S, Wereszczynski J, & Luger K (2021) Archaeal chromatin ‘slinkies’ are inherently dynamic complexes with deflected DNA wrapping pathways. Elife, 10. https://doi.org/10.7554/eLife.65587
Buchholz TO, Krull A, Shahidi R, Pigino G, Jekely G, Jug F (2019) Content-aware image restoration for electron microscopy. Methods Cell Biol 152:277–289. https://doi.org/10.1016/bs.mcb.2019.05.001
Buenrostro JD, Giresi PG, Zaba LC, Chang HY, Greenleaf WJ (2013) Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat Methods 10(12):1213–1218. https://doi.org/10.1038/nmeth.2688
Bui M, Dimitriadis EK, Hoischen C, An E, Quenet D, Giebe S, Nita-Lazar A, Diekmann S, Dalal Y (2012) Cell-cycle-dependent structural transitions in the human CENP-A nucleosome in vivo. Cell 150(2):317–326. https://doi.org/10.1016/j.cell.2012.05.035
Cai S, Böck D, Pilhofer M, Gan L (2018a) The in situ structures of mono-, di-, and trinucleosomes in human heterochromatin. Mol Biol Cell 29(20):2450–2457. https://doi.org/10.1091/mbc.E18-05-0331
Cai S, Song Y, Chen C, Shi J, Gan L (2018b) Natural chromatin is heterogeneous and self-associates in vitro. Mol Biol Cell 29(13):1652–1663. https://doi.org/10.1091/mbc.E17-07-0449
Cai S, Chen C, Tan ZY, Huang Y, Shi J, Gan L (2018c) Cryo-ET reveals the macromolecular reorganization of S. pombe mitotic chromosomes in vivo. Proc Natl Acad Sci USA 115:10977–10982. https://doi.org/10.1073/pnas.1720476115
Carone BR, Hung JH, Hainer SJ, Chou MT, Carone DM, Weng Z, Fazzio TG, Rando OJ (2014) High-resolution mapping of chromatin packaging in mouse embryonic stem cells and sperm. Dev Cell 30(1):11–22. https://doi.org/10.1016/j.devcel.2014.05.024
Chen M, Bell JM, Shi X, Sun SY, Wang Z, Ludtke SJ (2019) A complete data processing workflow for cryo-ET and subtomogram averaging. Nat Methods 16(11):1161–1168. https://doi.org/10.1038/s41592-019-0591-8
Chen M, Shi X, Yu Z, Fan G, Serysheva II, Baker ML, Luisi BF, Ludtke SJ, & Wang Z (2022) In situ structure of the AcrAB-TolC efflux pump at subnanometer resolution. Structure, 30(1), 107–113 e103 https://doi.org/10.1016/j.str.2021.08.008
Chereji RV, Morozov AV (2014) Ubiquitous nucleosome crowding in the yeast genome. Proc Natl Acad Sci U S A 111(14):5236–5241. https://doi.org/10.1073/pnas.1321001111
Chua EY, Vogirala VK, Inian O, Wong AS, Nordenskiold L, Plitzko JM, Danev R, Sandin S (2016) 3 9 A structure of the nucleosome core particle determined by phase-plate cryo-EM. Nucleic Acids Res 44(17):8013–8019. https://doi.org/10.1093/nar/gkw708
Danev R, Buijsse B, Khoshouei M, Plitzko JM, Baumeister W (2014) Volta potential phase plate for in-focus phase contrast transmission electron microscopy. Proc Natl Acad Sci U S A 111(44):15635–15640. https://doi.org/10.1073/pnas.1418377111
Davey CA, Sargent DF, Luger K, Maeder AW, Richmond TJ (2002) Solvent mediated interactions in the structure of the nucleosome core particle at 1 9 a resolution. J Mol Biol 319(5):1097–1113. https://doi.org/10.1016/S0022-2836(02)00386-8
David L, Huber W, Granovskaia M, Toedling J, Palm CJ, Bofkin L, Jones T, Davis RW, Steinmetz LM (2006) A high-resolution map of transcription in the yeast genome. Proc Natl Acad Sci U S A 103(14):5320–5325. https://doi.org/10.1073/pnas.0601091103
Davie JR, Saunders CA, Walsh JM, Weber SC (1981) Histone modifications in the yeast S. Cerevisiae Nucleic Acids Res 9(13):3205–3216. https://doi.org/10.1093/nar/9.13.3205
Dendooven T, Zhang Z, Yang J, McLaughlin SH, Schwab J, Scheres SHW, Yatskevich S, & Barford D (2022) Cryo-EM structure of the complete inner kinetochore of the budding yeast point centromere. bioRxiv
Dodonova SO, Zhu F, Dienemann C, Taipale J, Cramer P (2020) Nucleosome-bound SOX2 and SOX11 structures elucidate pioneer factor function. Nature 580(7805):669–672. https://doi.org/10.1038/s41586-020-2195-y
Ehara H, Kujirai T, Shirouzu M, Kurumizaka H, & Sekine SI (2022) Structural basis of nucleosome disassembly and reassembly by RNAPII elongation complex with FACT. Science, 377(6611) eabp9466 https://doi.org/10.1126/science.abp9466
Engeholm M, de Jager M, Flaus A, Brenk R, van Noort J, Owen-Hughes T (2009) Nucleosomes can invade DNA territories occupied by their neighbors. Nat Struct Mol Biol 16(2):151–158. https://doi.org/10.1038/nsmb.1551
Erdmann PS, Hou Z, Klumpe S, Khavnekar S, Beck F, Wilfling F, Plitzko JM, Baumeister W (2021) In situ cryo-electron tomography reveals gradient organization of ribosome biogenesis in intact nucleoli. Nat Commun 12(1):5364. https://doi.org/10.1038/s41467-021-25413-w
Farnung L, Vos SM, Wigge C, Cramer P (2017) Nucleosome-Chd1 structure and implications for chromatin remodelling. Nature 550(7677):539–542. https://doi.org/10.1038/nature24046
Filipovski M, Soffers JHM, Vos SM, Farnung L (2022) Structural basis of nucleosome retention during transcription elongation. Science 376(6599):1313–1316. https://doi.org/10.1126/science.abo3851
Fukuda Y, Laugks U, Lucic V, Baumeister W, Danev R (2015) Electron cryotomography of vitrified cells with a Volta phase plate. J Struct Biol 190(2):143–154. https://doi.org/10.1016/j.jsb.2015.03.004
Fukuda Y, Beck F, Plitzko JM, Baumeister W (2017) In situ structural studies of tripeptidyl peptidase II (TPPII) reveal spatial association with proteasomes. Proc Natl Acad Sci U S A 114(17):4412–4417. https://doi.org/10.1073/pnas.1701367114
Fukushima Y, Hatazawa S, Hirai S, Kujirai T, Ehara H, Sekine SI, Takizawa Y, Kurumizaka H (2022) Structural and biochemical analyses of the nucleosome containing Komagataella pastoris histones. J Biochem 172(2):79–88. https://doi.org/10.1093/jb/mvac043
Gan L, Ladinsky MS, Jensen GJ (2013) Chromatin in a marine picoeukaryote is a disordered assemblage of nucleosomes. Chromosoma 122(5):377–386. https://doi.org/10.1007/s00412-013-0423-z
Gansen A, Toth K, Schwarz N, Langowski J (2015) Opposing roles of H3- and H4-acetylation in the regulation of nucleosome structure–a FRET study. Nucleic Acids Res 43(3):1433–1443. https://doi.org/10.1093/nar/gku1354
Garel A, Axel R (1976) Selective digestion of transcriptionally active ovalbumin genes from oviduct nuclei. Proc Natl Acad Sci U S A 73(11):3966–3970. https://doi.org/10.1073/pnas.73.11.3966
Goffeau A, Barrell, BG, Bussey H, Davis RW, Dujon B, Feldmann H, Galibert F, Hoheisel JD, Jacq C, Johnston M, Louis EJ, Mewes HW, Murakami Y, Philippsen P, Tettelin H, & Oliver SG (1996) Life with 6000 genes. Science, 274(5287), 546, 563–547. https://www.ncbi.nlm.nih.gov/pubmed/8849441
Guan R, Lian T, Zhou BR, He E, Wu C, Singleton M, Bai Y (2021) Structural and dynamic mechanisms of CBF3-guided centromeric nucleosome formation. Nat Commun 12(1):1763. https://doi.org/10.1038/s41467-021-21985-9
Harastani M, Eltsov M, Leforestier A, Jonic S (2021) HEMNMA-3D: cryo electron tomography method based on normal mode analysis to study continuous conformational variability of macromolecular complexes. Front Mol Biosci 8:663121. https://doi.org/10.3389/fmolb.2021.663121
Henikoff JG, Belsky JA, Krassovsky K, MacAlpine DM, Henikoff S (2011) Epigenome characterization at single base-pair resolution. Proc Natl Acad Sci U S A 108(45):18318–18323. https://doi.org/10.1073/pnas.1110731108
Hereford LM, Rosbash M (1977) Number and distribution of polyadenylated RNA sequences in yeast. Cell 10(3):453–462. https://doi.org/10.1016/0092-8674(77)90032-0
Himes BA, Zhang P (2018) emClarity: software for high-resolution cryo-electron tomography and subtomogram averaging. Nat Methods 15(11):955–961. https://doi.org/10.1038/s41592-018-0167-z
Hirano R, Arimura Y, Kujirai T, Shibata M, Okuda A, Morishima K, Inoue R, Sugiyama M, & Kurumizaka H (2021) Histone variant H2A.B-H2B dimers are spontaneously exchanged with canonical H2A-H2B in the nucleosome. Commun Biol, 4(1), 191 https://doi.org/10.1038/s42003-021-01707-z
Hoffmann PC, Kreysing JP, Khusainov I, Tuijtel MW, Welsch S, Beck M (2022) Structures of the eukaryotic ribosome and its translational states in situ. Nat Commun 13(1):7435. https://doi.org/10.1038/s41467-022-34997-w
Huang C, Zhang Z, Xu M, Li Y, Li Z, Ma Y, Cai T, Zhu B (2013) H3 3–H4 tetramer splitting events feature cell-type specific enhancers. PLoS Genet 9(6):e1003558. https://doi.org/10.1371/journal.pgen.1003558
Hylton RK, & Swulius MT (2021) Challenges and triumphs in cryo-electron tomography. iScience, 24 (9) 102959 https://doi.org/10.1016/j.isci.2021.102959
Ishida H, & Kono H (2021) Torsional stress can regulate the unwrapping of two outer half superhelical turns of nucleosomal DNA. Proc Natl Acad Sci U S A, 118(7) https://doi.org/10.1073/pnas.2020452118
Ishida H, Kono H (2022) Free energy landscape of H2A–H2B displacement from nucleosome. J Mol Biol 434(16):167707. https://doi.org/10.1016/j.jmb.2022.167707
Jamai A, Imoberdorf RM, Strubin M (2007) Continuous histone H2B and transcription-dependent histone H3 exchange in yeast cells outside of replication. Mol Cell 25(3):345–355. https://doi.org/10.1016/j.molcel.2007.01.019
Johnson SM, Tan FJ, McCullough HL, Riordan DP, Fire AZ (2006) Flexibility and constraint in the nucleosome core landscape of Caenorhabditis elegans chromatin. Genome Res 16(12):1505–1516. https://doi.org/10.1101/gr.5560806
Katan-Khaykovich Y, Struhl K (2011) Splitting of H3–H4 tetramers at transcriptionally active genes undergoing dynamic histone exchange. Proc Natl Acad Sci U S A 108(4):1296–1301. https://doi.org/10.1073/pnas.1018308108
Kato D, Osakabe A, Arimura Y, Mizukami Y, Horikoshi N, Saikusa K, Akashi S, Nishimura Y, Park SY, Nogami J, Maehara K, Ohkawa Y, Matsumoto A, Kono H, Inoue R, Sugiyama M, Kurumizaka H (2017) Crystal structure of the overlapping dinucleosome composed of hexasome and octasome. Science 356(6334):205–208. https://doi.org/10.1126/science.aak9867
Kimura H, Cook PR (2001) Kinetics of core histones in living human cells: little exchange of H3 and H4 and some rapid exchange of H2B. J Cell Biol 153(7):1341–1353. https://doi.org/10.1083/jcb.153.7.1341
Konrad SF, Vanderlinden W, Frederickx W, Brouns T, Menze BH, De Feyter S, Lipfert J (2021) High-throughput AFM analysis reveals unwrapping pathways of H3 and CENP-A nucleosomes. Nanoscale 13(10):5435–5447. https://doi.org/10.1039/d0nr08564b
Konrad SF, Vanderlinden W, Lipfert J (2022) Quantifying epigenetic modulation of nucleosome breathing by high-throughput AFM imaging. Biophys J 121(5):841–851. https://doi.org/10.1016/j.bpj.2022.01.014
Kurumizaka H, Kujirai T, Takizawa Y (2021) Contributions of histone variants in nucleosome structure and function. J Mol Biol 433(6):166678. https://doi.org/10.1016/j.jmb.2020.10.012
Lancrey A, Joubert A, Duvernois-Berthet E, Routhier E, Raj S, Thierry A, Sigarteu M, Ponger L, Croquette V, Mozziconacci J, Boule JB (2022) Nucleosome positioning on large tandem DNA repeats of the ‘601’ sequence engineered in Saccharomyces cerevisiae. J Mol Biol 434(7):167497. https://doi.org/10.1016/j.jmb.2022.167497
Lavelle C, Prunell A (2007) Chromatin polymorphism and the nucleosome superfamily: a genealogy. Cell Cycle 6(17):2113–2119. https://doi.org/10.4161/cc.6.17.4631
Lee MS, Garrard WT (1991a) Positive DNA supercoiling generates a chromatin conformation characteristic of highly active genes. Proc Natl Acad Sci U S A 88(21):9675–9679. https://doi.org/10.1073/pnas.88.21.9675
Lee MS, Garrard WT (1991b) Transcription-induced nucleosome ‘splitting’: an underlying structure for DNase I sensitive chromatin. EMBO J 10(3):607–615. https://doi.org/10.1002/j.1460-2075.1991.tb07988.x
Lee KP, Baxter HJ, Guillemette JG, Lawford HG, Lewis PN (1982) Structural studies on yeast nucleosomes. Can J Biochem 60(3):379–388. https://doi.org/10.1139/o82-045
Lee JY, Wei S, Lee TH (2011) Effects of histone acetylation by Piccolo NuA4 on the structure of a nucleosome and the interactions between two nucleosomes. J Biol Chem 286(13):11099–11109. https://doi.org/10.1074/jbc.M110.192047
Leung A, Cheema M, Gonzalez-Romero R, Eirin-Lopez JM, Ausio J, Nelson CJ (2016) Unique yeast histone sequences influence octamer and nucleosome stability. FEBS Lett 590(16):2629–2638. https://doi.org/10.1002/1873-3468.12266
Levchenko V, Jackson B, Jackson V (2005) Histone release during transcription: displacement of the two H2A–H2B dimers in the nucleosome is dependent on different levels of transcription-induced positive stress. Biochemistry 44(14):5357–5372. https://doi.org/10.1021/bi047786o
Liu LF, Wang JC (1987) Supercoiling of the DNA template during transcription. Proc Natl Acad Sci U S A 84(20):7024–7027. https://doi.org/10.1073/pnas.84.20.7024
Lohr D, Hereford L (1979) Yeast chromatin is uniformly digested by DNase-I. Proc Natl Acad Sci U S A 76(9):4285–4288. https://doi.org/10.1073/pnas.76.9.4285
Lohr D, Kovacic RT, Van Holde KE (1977) Quantitative analysis of the digestion of yeast chromatin by staphylococcal nuclease. Biochemistry 16(3):463–471. https://doi.org/10.1021/bi00622a020
Lowary PT, Widom J (1998) New DNA sequence rules for high affinity binding to histone octamer and sequence-directed nucleosome positioning. J Mol Biol 276(1):19–42. https://doi.org/10.1006/jmbi.1997.1494
Luger K, Mader AW, Richmond RK, Sargent DF, Richmond TJ (1997) Crystal structure of the nucleosome core particle at 28 A resolution. Nature 389(6648):251–260. https://doi.org/10.1038/38444
Markert J, Luger K (2021) Nucleosomes meet their remodeler match. Trends Biochem Sci 46(1):41–50. https://doi.org/10.1016/j.tibs.2020.08.010
Melters DP, Pitman M, Rakshit T, Dimitriadis EK, Bui M, Papoian GA, Dalal Y (2019) Intrinsic elasticity of nucleosomes is encoded by histone variants and calibrated by their binding partners. Proc Natl Acad Sci U S A 116(48):24066–24074. https://doi.org/10.1073/pnas.1911880116
Migl D, Kschonsak M, Arthur CP, Khin Y, Harrison SC, Ciferri C, Dimitrova YN (2020) Cryoelectron microscopy structure of a yeast centromeric nucleosome at 27 A resolution. Structure 28(3):363–370. https://doi.org/10.1016/j.str.2019.12.002
Nagalakshmi U, Wang Z, Waern K, Shou C, Raha D, Gerstein M, Snyder M (2008) The transcriptional landscape of the yeast genome defined by RNA sequencing. Science 320(5881):1344–1349. https://doi.org/10.1126/science.1158441
Neumann H, Hancock SM, Buning R, Routh A, Chapman L, Somers J, Owen-Hughes T, van Noort J, Rhodes D, Chin JW (2009) A method for genetically installing site-specific acetylation in recombinant histones defines the effects of H3 K56 acetylation. Mol Cell 36(1):153–163. https://doi.org/10.1016/j.molcel.2009.07.027
Ng CT, Gan L (2020) Investigating eukaryotic cells with cryo-ET. Mol Biol Cell 31(2):87–100. https://doi.org/10.1091/mbc.E18-05-0329
Noble AJ, Dandey VP, Wei H, Brasch J, Chase J, Acharya P, Tan Y Z, Zhang Z, Kim LY, Scapin G, Rapp M, Eng ET, Rice WJ, Cheng A, Negro CJ, Shapiro L, Kwong PD, Jeruzalmi D, des Georges A, Carragher B (2018) Routine single particle CryoEM sample and grid characterization by tomography. Elife, 7. https://doi.org/10.7554/eLife.34257
Noll M, Kornberg RD (1977) Action of micrococcal nuclease on chromatin and the location of histone H1. J Mol Biol 109(3):393–404. https://doi.org/10.1016/s0022-2836(77)80019-3
Nozawa K, Takizawa Y, Pierrakeas L, Sogawa-Fujiwara C, Saikusa K, Akashi S, Luk E, Kurumizaka H (2022) Cryo-electron microscopy structure of the H3–H4 octasome: a nucleosome-like particle without histones H2A and H2B. Proc Natl Acad Sci U S A 119(45):e2206542119. https://doi.org/10.1073/pnas.2206542119
Ohno M, Ando T, Priest D G, Kumar V, Yoshida Y, & Taniguchi Y (2019) Sub-nucleosomal genome structure reveals distinct nucleosome folding motifs. Cell, 176(3), 520–534 e525 https://doi.org/10.1016/j.cell.2018.12.014
Patterton HG, Landel CC, Landsman D, Peterson CL, Simpson RT (1998) The biochemical and phenotypic characterization of Hho1p, the putative linker histone H1 of Saccharomyces cerevisiae. J Biol Chem 273(13):7268–7276. https://doi.org/10.1074/jbc.273.13.7268
Perales R, Zhang L, Bentley D (2011) Histone occupancy in vivo at the 601 nucleosome binding element is determined by transcriptional history. Mol Cell Biol 31(16):3485–3496. https://doi.org/10.1128/MCB.05599-11
Pineiro M, Puerta C, Palacian E (1991) Yeast nucleosomal particles: structural and transcriptional properties. Biochemistry 30(23):5805–5810. https://doi.org/10.1021/bi00237a025
Poge M, Mahamid J, Imanishi SS, Plitzko JM, Palczewski K, & Baumeister W (2021) Determinants shaping the nanoscale architecture of the mouse rod outer segment. Elife, 10 https://doi.org/10.7554/eLife.72817
Punjani A, Fleet DJ (2021) 3D variability analysis: resolving continuous flexibility and discrete heterogeneity from single particle cryo-EM. J Struct Biol 213(2):107702. https://doi.org/10.1016/j.jsb.2021.107702
Ramachandran S, Ahmad K, & Henikoff S (2017) Transcription and remodeling produce asymmetrically unwrapped nucleosomal intermediates. Mol Cell, 68(6) 1038–1053 e1034 https://doi.org/10.1016/j.molcel.2017.11.015
Ramani V, Qiu R, & Shendure J (2019) High sensitivity profiling of chromatin structure by MNase-SSP. Cell Rep, 26 9 2465–2476 e2464 https://doi.org/10.1016/j.celrep.2019.02.007
Rhee HS, Bataille AR, Zhang L, Pugh BF (2014) Subnucleosomal structures and nucleosome asymmetry across a genome. Cell 159(6):1377–1388. https://doi.org/10.1016/j.cell.2014.10.054
Roulland Y, Ouararhni K, Naidenov M, Ramos L, Shuaib M, Syed SH, Lone IN, Boopathi R, Fontaine E, Papai G, Tachiwana H, Gautier T, Skoufias D, Padmanabhan K, Bednar J, Kurumizaka H, Schultz P, Angelov D, Hamiche A, Dimitrov S (2016) The flexible ends of CENP-A nucleosome are required for mitotic fidelity. Mol Cell 63(4):674–685. https://doi.org/10.1016/j.molcel.2016.06.023
Rufiange A, Jacques PE, Bhat W, Robert F, Nourani A (2007) Genome-wide replication-independent histone H3 exchange occurs predominantly at promoters and implicates H3 K56 acetylation and Asf1. Mol Cell 27(3):393–405. https://doi.org/10.1016/j.molcel.2007.07.011
Sato S, Takizawa Y, Hoshikawa F, Dacher M, Tanaka H, Tachiwana H, Kujirai T, Iikura Y, Ho CH, Adachi N, Patwal I, Flaus A, Kurumizaka H (2021) Cryo-EM structure of the nucleosome core particle containing Giardia lamblia histones. Nucleic Acids Res 49(15):8934–8946. https://doi.org/10.1093/nar/gkab644
Schuller AP, Wojtynek M, Mankus D, Tatli M, Kronenberg-Tenga R, Regmi SG, Dip PV, Lytton-Jean AKR, Brignole EJ, Dasso M, Weis K, Medalia O, Schwartz TU (2021) The cellular environment shapes the nuclear pore complex architecture. Nature 598(7882):667–671. https://doi.org/10.1038/s41586-021-03985-3
Schur FK (2019) Toward high-resolution in situ structural biology with cryo-electron tomography and subtomogram averaging. Curr Opin Struct Biol 58:1–9. https://doi.org/10.1016/j.sbi.2019.03.018
Schwartz O, Axelrod JJ, Campbell SL, Turnbaugh C, Glaeser RM, Muller H (2019) Laser phase plate for transmission electron microscopy. Nat Methods 16(10):1016–1020. https://doi.org/10.1038/s41592-019-0552-2
Simon JM, Giresi PG, Davis IJ, Lieb JD (2012) Using formaldehyde-assisted isolation of regulatory elements (FAIRE) to isolate active regulatory DNA. Nat Protoc 7(2):256–267. https://doi.org/10.1038/nprot.2011.444
Sinha KK, Gross JD, & Narlikar GJ (2017) Distortion of histone octamer core promotes nucleosome mobilization by a chromatin remodeler. Science 355(6322) https://doi.org/10.1126/science.aaa3761
Sokolova V, Sarkar S, Tan D (2023) Histone variants and chromatin structure, update of advances. Comput Struct Biotechnol J 21:299–311. https://doi.org/10.1016/j.csbj.2022.12.002
Sollner-Webb B, Felsenfeld G (1975) A comparison of the digestion of nuclei and chromatin by staphylococcal nuclease. Biochemistry 14(13):2915–2920. https://doi.org/10.1021/bi00684a019
Soman A, Wong SY, Korolev N, Surya W, Lattmann S, Vogirala VK, Chen Q, Berezhnoy NV, van Noort J, Rhodes D, Nordenskiold L (2022) Columnar structure of human telomeric chromatin. Nature 609(7929):1048–1055. https://doi.org/10.1038/s41586-022-05236-5
Song L, & Crawford GE (2010) DNase-seq: a high-resolution technique for mapping active gene regulatory elements across the genome from mammalian cells. Cold Spring Harb Protoc, 2010(2), pdb prot5384. https://doi.org/10.1101/pdb.prot5384
Stewart-Morgan KR, Petryk N, Groth A (2020) Chromatin replication and epigenetic cell memory. Nat Cell Biol 22(4):361–371. https://doi.org/10.1038/s41556-020-0487-y
Szent-Gyorgyi C, Isenberg I (1983) The organization of oligonucleosomes in yeast. Nucleic Acids Res 11(11):3717–3736. https://doi.org/10.1093/nar/11.11.3717
Tachiwana H, Kagawa W, Shiga T, Osakabe A, Miya Y, Saito K, Hayashi-Takanaka Y, Oda T, Sato M, Park SY, Kimura H, Kurumizaka H (2011) Crystal structure of the human centromeric nucleosome containing CENP-A. Nature 476(7359):232–235. https://doi.org/10.1038/nature10258
Takizawa Y, Tanaka H, Machida S, Koyama M, Maehara K, Ohkawa Y, Wade PA, Wolf M, & Kurumizaka H (2018) Cryo-EM structure of the nucleosome containing the ALB1 enhancer DNA sequence. Open Biol, 8(3) https://doi.org/10.1098/rsob.170255
Takizawa Y, Ho CH, Tachiwana H, Matsunami H, Kobayashi W, Suzuki M, Arimura Y, Hori T, Fukagawa T, Ohi MD, Wolf M, & Kurumizaka H (2020) Cryo-EM structures of centromeric tri-nucleosomes containing a central CENP-A nucleosome. Structure, 28(1), 44–53 e44 https://doi.org/10.1016/j.str.2019.10.016
Takizawa Y, Kurumizaka H (2022) Chromatin structure meets cryo-EM: dynamic building blocks of the functional architecture. Biochim Biophys Acta Gene Regul Mech 1865(7):194851. https://doi.org/10.1016/j.bbagrm.2022.194851
Tan S, Davey CA (2011) Nucleosome structural studies. Curr Opin Struct Biol 21(1):128–136. https://doi.org/10.1016/j.sbi.2010.11.006
Tan, Z. Y., Cai, S., Noble, A. J., Chen, J. K., Shi, J., & Gan, L. (2021). Heterogeneous non-canonical nucleosomes predominate in yeast cells in situ. bioRxiv.
Tegunov D, Xue L, Dienemann C, Cramer P, Mahamid J (2021) Multi-particle cryo-EM refinement with M visualizes ribosome-antibiotic complex at 3 5 A in cells. Nat Methods 18(2):186–193. https://doi.org/10.1038/s41592-020-01054-7
Thomas JO, Furber V (1976) Yeast chromatin structure. FEBS Lett 66(2):274–280. https://doi.org/10.1016/0014-5793(76)80521-2
Torne J, Ray-Gallet D, Boyarchuk E, Garnier M, Le Baccon P, Coulon A, Orsi GA, Almouzni G (2020) Two HIRA-dependent pathways mediate H3 3 de novo deposition and recycling during transcription. Nat Struct Mol Biol 27(11):1057–1068. https://doi.org/10.1038/s41594-020-0492-7
Ulyanova NP, Schnitzler GR (2005) Human SWI/SNF generates abundant, structurally altered dinucleosomes on polynucleosomal templates. Mol Cell Biol 25(24):11156–11170. https://doi.org/10.1128/MCB.25.24.11156-11170.2005
Ushinsky SC, Bussey H, Ahmed AA, Wang Y, Friesen J, Williams BA, Storms RK (1997) Histone H1 in Saccharomyces cerevisiae. Yeast 13(2):151–161. https://doi.org/10.1002/(SICI)1097-0061(199702)13:2%3c151::AID-YEA94%3e3.0.CO;2-5
Waterborg JH (2000) Steady-state levels of histone acetylation in Saccharomyces cerevisiae. J Biol Chem 275(17):13007–13011. https://doi.org/10.1074/jbc.275.17.13007
Weiner A, Hughes A, Yassour M, Rando OJ, Friedman N (2010) High-resolution nucleosome mapping reveals transcription-dependent promoter packaging. Genome Res 20(1):90–100. https://doi.org/10.1101/gr.098509.109
Weintraub H, Groudine M (1976) Chromosomal subunits in active genes have an altered conformation. Science 193(4256):848–856. https://doi.org/10.1126/science.948749
White CL, Suto RK, Luger K (2001) Structure of the yeast nucleosome core particle reveals fundamental changes in internucleosome interactions. EMBO J 20(18):5207–5218. https://doi.org/10.1093/emboj/20.18.5207
Woodcock CL, Skoultchi AI, Fan Y (2006) Role of linker histone in chromatin structure and function: H1 stoichiometry and nucleosome repeat length. Chromosome Res 14(1):17–25. https://doi.org/10.1007/s10577-005-1024-3
Xue L, Lenz S, Zimmermann-Kogadeeva M, Tegunov D, Cramer P, Bork P, Rappsilber J, Mahamid J (2022) Visualizing translation dynamics at atomic detail inside a bacterial cell. Nature 610(7930):205–211. https://doi.org/10.1038/s41586-022-05255-2
Zhang P (2019) Advances in cryo-electron tomography and subtomogram averaging and classification. Curr Opin Struct Biol 58:249–258. https://doi.org/10.1016/j.sbi.2019.05.021
Zhong ED, Bepler T, Berger B, Davis JH (2021) CryoDRGN: reconstruction of heterogeneous cryo-EM structures using neural networks. Nat Methods 18(2):176–185. https://doi.org/10.1038/s41592-020-01049-4
Zhou BR, Jiang J, Feng H, Ghirlando R, Xiao TS, Bai Y (2015) Structural mechanisms of nucleosome recognition by linker histones. Mol Cell 59(4):628–638. https://doi.org/10.1016/j.molcel.2015.06.025
Zhou BR, Yadav KNS, Borgnia M, Hong J, Cao B, Olins AL, Olins DE, Bai Y, Zhang P (2019a) Atomic resolution cryo-EM structure of a native-like CENP-A nucleosome aided by an antibody fragment. Nat Commun 10(1):2301. https://doi.org/10.1038/s41467-019-10247-4
Zhou K, Gaullier G, Luger K (2019b) Nucleosome structure and dynamics are coming of age. Nat Struct Mol Biol 26(1):3–13. https://doi.org/10.1038/s41594-018-0166-x
Zhou M, Dai L, Li C, Shi L, Huang Y, Guo Z, Wu F, Zhu P, & Zhou Z (2021) Structural basis of nucleosome dynamics modulation by histone variants H2A. B and H2A. Z 22 EMBO J, 40(1) e105907 https://doi.org/10.15252/embj.2020105907
Zivanov J, Oton J, Ke Z, von Kugelgen A, Pyle E, Qu K, Morado D, Castano-Diez D, Zanetti G, Bharat T AM, Briggs JAG, & Scheres SHW (2022) A Bayesian approach to single-particle electron cryo-tomography in RELION-4.0. Elife, 11. https://doi.org/10.7554/eLife.83724
Zlatanova J, Bishop TC, Victor JM, Jackson V, van Holde K (2009) The nucleosome family: dynamic and growing. Structure 17(2):160–171. https://doi.org/10.1016/j.str.2008.12.016
Acknowledgements
We thank Drs. E.Y.D. Chua, M. Halic, Y. Cheng, Z. Zhou, L. Dai, P. Cramer, S. Dodonova, H. Kurumizaka, T. Kujirai, L. Nordenskiöld, A. Soman and L. Farnung for sharing high-resolution figures.
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CYYC and LG were supported by a Singapore Ministry of Education Tier 2 grant MOE2019-T2-1–140.
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Chong, C.Y.Y., Gan, L. Are extraordinary nucleosome structures more ordinary than we thought?. Chromosoma 132, 139–152 (2023). https://doi.org/10.1007/s00412-023-00791-w
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DOI: https://doi.org/10.1007/s00412-023-00791-w