A Condensed History of Chromatin Research

  • Kirti PrakashEmail author
Part of the Springer Theses book series (Springer Theses)


The cell nucleus is a discernible cellular compartment, where the expression and regulation of genes take place. Due to limited tools and methods, it remained ignored for a long time (until the late 19th century), however nowadays it is a major research topic.


Germinal Vesicle Chromatin Domain Chromosome Territory Chromatin Loop Chromatin Architecture 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This chapter is an outcome of many discussions with David Fournier, who has helped immensely in formulating and revising the text.


  1. Albiez H, Cremer M, Tiberi C, Vecchio L, Schermelleh L, Dittrich S, Küpper K, Joffe B, Thormeyer T, von Hase J et al (2006) Chromatin domains and the interchromatin compartment form structurally defined and functionally interacting nuclear networks. Chromosom Res 14(7):707–733Google Scholar
  2. Allfrey VG, Faulkner R, Mirsky AE (1964) Acetylation and methylation of histones and their possible role in the regulation of rna synthesis. Proc Natl Academy Sci United States Am 51(5):786Google Scholar
  3. Avery OT, MacLeod CM, McCarty M (1944) Studies on the chemical nature of the substance inducing transformation of pneumococcal types induction of transformation by a desoxyribonucleic acid fraction isolated from pneumococcus type iii. J Exp Med 79(2):137–158Google Scholar
  4. Axelrod D, Koppel DE, Schlessinger J, Elson Ei, Webb WW (1976) Mobility measurement by analysis of fluorescence photobleaching recovery kinetics. Biophys J 16(9):1976Google Scholar
  5. Baker JR (1949) The cell-theory: a restatement, history, and critique. Q J Microsc Sci 3(9):87–108Google Scholar
  6. Barbieri M, Chotalia M, Fraser J, Lavitas L-M, Dostie J, Pombo A, Nicodemi M (2012) Complexity of chromatin folding is captured by the strings and binders switch model. Proc Natl Academy Sci 109(40):16173–16178CrossRefGoogle Scholar
  7. Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, Wei G, Chepelev I, Zhao K (2007) High-resolution profiling of histone methylations in the human genome. Cell 129(4):823–837CrossRefPubMedGoogle Scholar
  8. Beadle GW, Tatum EL (1941) Genetic control of biochemical reactions in neurospora. Proc Natl Academy Sci United States Am 27(11):499Google Scholar
  9. Berezney R, Coffey DS (1976) The nuclear protein matrix: isolation, structure, and functions. Advances Enzyme Regul 14:63–100Google Scholar
  10. Betzig E (1995) Proposed method for molecular optical imaging. Opt Lett 20(3):237–239Google Scholar
  11. Betzig E, Patterson GH, Sougrat R, Lindwasser OW, Olenych S, Bonifacino JS, Davidson MW, Lippincott-Schwartz J, Hess HF (2006) Imaging intracellular fluorescent proteins at nanometer resolution. Science 313(5793):1642–1645Google Scholar
  12. Boettiger AN, Bintu B, Moffitt JR, Wang S, Beliveau BJ, Fudenberg G, Imakaev M, Mirny LA, Wu C-T, Zhuang X (2016) Super-resolution imaging reveals distinct chromatin folding for different epigenetic states. Nature 529(7586):418–422Google Scholar
  13. Boveri T (1888) Zellen-Studien: Die Befruchtung und Teilung des Eies von Ascaris megalocephala. Verlag von Gustav FischerGoogle Scholar
  14. Boveri T (1904) Ergebnisse über die Konstitution der chromatischen Substanz des Zellkerns. Verlag von Gustav Fischer in JenaGoogle Scholar
  15. Boveri T (1909) Die Blastomerenkerne von Ascaris megalocephala und die Theorie der Chromosomenindividualität. EngelmannGoogle Scholar
  16. Branco MR, Pombo A (2006) Intermingling of chromosome territories in interphase suggests role in translocations and transcription-dependent associations. PLoS Biol 4(5):e138Google Scholar
  17. Busch H (1974) The cell nucleus. Academic Press, New YorkGoogle Scholar
  18. Chakalova L, Debrand E, Mitchell JA, Osborne CS, Fraser P (2005) Replication and transcription: shaping the landscape of the genome. Nature Rev Genet 6(9):669–677Google Scholar
  19. Chandra T, Kirschner K, Thuret J-Y, Pope BD, Ryba T, Newman S, Ahmed K, Samarajiwa SA, Salama R, Carroll T et al (2012) Independence of repressive histone marks and chromatin compaction during senescent heterochromatic layer formation. Molecular cell 47(2):203–214CrossRefPubMedPubMedCentralGoogle Scholar
  20. Chargaff E, Lipshitz R, Green C (1952) Composition of the desoxypentose nucleic acids of four genera of sea-urchin. J Biol Chem 195(1):155–160Google Scholar
  21. Comings DE (1980) Arrangement of chromatin in the nucleus. Hum Genet 53(2):131–143Google Scholar
  22. Cremer T, Cremer C (2001) Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nature Rev Genet 2(4):292–301Google Scholar
  23. Cremer T, Cremer C (2009a) Rise, fall and resurrection of chromosome territories: a historical perspective part ii. fall and resurrection of chromosome territories during the 1950s to 1980s. part iii. chromosome territories and the functional nuclear architecture: experiments and m. Eur J Histochem 50(4):223–272Google Scholar
  24. Cremer T, Cremer C (2009b) Rise, fall and resurrection of chromosome territories: a historical perspective. part i. the rise of chromosome territories. Eur J Histochem 50(3):161–176Google Scholar
  25. Cremer T, Cremer C, Baumann H, Luedtke EK, Sperling K, Teuber V, Zorn C (1982a) Rabl’s model of the interphase chromosome arrangement tested in chinise hamster cells by premature chromosome condensation and laser-uv-microbeam experiments. Hum Genet 60(1):46–56Google Scholar
  26. Cremer T, Cremer C, Schneider T, Baumann H, Hens L, Kirsch-Volders M (1982b) Analysis of chromosome positions in the interphase nucleus of chinese hamster cells by laser-uv-microirradiation experiments. Hum Genet 62(3):201–209Google Scholar
  27. Cremer T, Küpper K, Dietzel S, Fakan S (2004) Higher order chromatin architecture in the cell nucleus: on the way from structure to function. Biol Cell 96(8):555–567Google Scholar
  28. Cremer T, Cremer M, Hübner B, Strickfaden H, Smeets D, Popken J, Sterr M, Markaki Y, Rippe K, Cremer C (2015) The 4d nucleome: Evidence for a dynamic nuclear landscape based on co-aligned active and inactive nuclear compartments. FEBS LettGoogle Scholar
  29. Crick F, Barnett L, Brenner S, Watts-Tobin RJ (1961) General nature of the genetic code for proteins. Macmillan J LtdGoogle Scholar
  30. Dahm R (2008) Discovering dna: Friedrich miescher and the early years of nucleic acid research. Hum genet 122(6):565–581Google Scholar
  31. Dekker J, Rippe K, Dekker M, Kleckner N (2002) Capturing chromosome conformation. Science 295(5558):1306–1311Google Scholar
  32. Fakan S (2004) The functional architecture of the nucleus as analysed by ultrastructural cytochemistry. Histochem Cell Biol 122(2):83–93Google Scholar
  33. Ficq A, Pavan C (1957) Autoradiography of polytene chromosomes of rhynchosciara angelae at different stages of larval developmentGoogle Scholar
  34. Flemming W (1882) 1: Beiträge zur kenntnis der zelle und ihrer lebenserscheinungen. iii. Teil. Arch. f. mikr. Anat., Bd 20Google Scholar
  35. Gall JG (1968a) Differential synthesis of the genes for ribosomal rna during amphibian oögenesis. Proc Natl Academy Sci United States Am 60(2):553Google Scholar
  36. Gall JG (1968b) The genes for ribosomal rna during oogenesis. Genetics 61 (1): Suppl–121Google Scholar
  37. Gall JG, Pardue ML (1969) Formation and detection of rna-dna hybrid molecules in cytological preparations. Proc Natl Academy Sci 63(2):378–383Google Scholar
  38. Gurdon JB, Elsdale TR, Fischberg M (1958) Sexually mature individuals of xenopus laevis from the transplantation of single somatic nucleiGoogle Scholar
  39. Gustafsson MGL (2000) Surpassing the lateral resolution limit by a factor of two using structured illumination microscopy. J Microsc 198(2):82–87Google Scholar
  40. Heintzmann R, Cremer C (1999) Laterally modulated excitation microscopy: improvement of resolution by using a diffraction grating. In: international society for optics and photonics BiOS Europe’98, pp 185–196Google Scholar
  41. Hell SW, Wichmann J (1994) Breaking the diffraction resolution limit by stimulated emission: stimulated-emission-depletion fluorescence microscopy. Opt Lett 19(11):780–782Google Scholar
  42. Hertwig O (1875) Beiträge zur kenntniss der bildung, befruchtung und theilung des thierischen eies... W. EngelmannGoogle Scholar
  43. Hertwig O (1898) Lehrbuch der Entwicklungsgeschichte des Menschen und der Wirbelthiere. G. FischerGoogle Scholar
  44. Hess SL, Girirajan TPK, Mason MD (2006) Ultra-high resolution imaging by fluorescence photoactivation localization microscopy. Biophys J 91(11):4258Google Scholar
  45. Hurwitz J (2005) The discovery of rna polymerase. J Biol Chem 280(52):42477–42485Google Scholar
  46. Jacob F, Monod J (1961) Genetic regulatory mechanisms in the synthesis of proteins. J Mol Biol 3(3):318–356Google Scholar
  47. Karsenti E (2008) Self-organization in cell biology: a brief history. Nature Rev Mol Cell Biol 9(3):255–262CrossRefGoogle Scholar
  48. Kossel A (1883) Zur chemie des zellkerns. Zeitschrift für physiologische Chemie 7(1):7–22Google Scholar
  49. Kossel A (1884) Ueber einen peptonartigen bestandtheil des zellkerns. Zeitschrift für physiologische Chemie 8(6):511–515Google Scholar
  50. Kossel A, Kennaway EL (1911) Über nitroclupein. Hoppe-Seyler’s Zeitschrift für physiologische Chemie 72(5–6):486–489Google Scholar
  51. Kozak M (1984) Compilation and analysis of sequences upstream from the translational start site in eukaryotic mrnas. Nucl Acids Res 12(2):857–872Google Scholar
  52. Lanctôt C, Cheutin T, Cremer M, Cavalli G, Cremer T (2007) Dynamic genome architecture in the nuclear space: regulation of gene expression in three dimensions. Nature Rev Genet 8(2):104–115Google Scholar
  53. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W et al (2001) Initial sequencing and analysis of the human genome. Nature 409(6822):860–921Google Scholar
  54. Langer-Safer PR, Levine M, Ward DC (1982) Immunological method for mapping genes on drosophila polytene chromosomes. Proc Natl Academy Sci 79(14):4381–4385Google Scholar
  55. Lemmer P, Gunkel M, Baddeley D, Kaufmann R, Urich A, Weiland Y, Reymann J, Müller P, Hausmann M, Cremer C (2008) Spdm: light microscopy with single-molecule resolution at the nanoscale. Appl Phys B 93(1):1–12Google Scholar
  56. Lengauer C, Green ED, Cremer T (1992) Fluorescence in situ hybridization of yac clones after alu-pcr amplification. Genomics 13(3):826–828Google Scholar
  57. Lewis EB (1945) The relation of repeats to position effect in drosophila melanogaster. Genetics 30(2):137Google Scholar
  58. Lidke K, Rieger B, Jovin T, Heintzmann R (2005) Superresolution by localization of quantum dots using blinking statistics. Opt Express 13(18):7052–7062CrossRefPubMedGoogle Scholar
  59. Lieberman-Aiden E, van Berkum NL, Williams L, Imakaev M, Ragoczy T, Telling A, Amit I, Lajoie BR, Sabo PJ, Dorschner MO et al (2009) Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326(5950):289–293Google Scholar
  60. Lomvardas S, Barnea G, Pisapia DJ, Mendelsohn M, Kirkland J, Axel R (2006) Interchromosomal interactions and olfactory receptor choice. Cell 126(2):403–413Google Scholar
  61. Ma H, Samarabandu J, Devdhar RS, Acharya R, Cheng P-C, Meng C, Berezney R (1998) Spatial and temporal dynamics of dna replication sites in mammalian cells. J Cell Biol 143(6):1415–1425Google Scholar
  62. Meehan RR, Lewis JD, McKay S, Kleiner EL, Bird AP (1989) Identification of a mammalian protein that binds specifically to dna containing methylated cpgs. Cell 58(3):499–507Google Scholar
  63. Miescher F (1871) Hoppe-seyler’s medicinisch-chemische untersuchungen. Ueber die chemische Zusammensetzung der Eiterzellen 4:441-460Google Scholar
  64. Miescher F (1874) Die Spermatozoen einiger Wirbelthiere: ein Beitrag zur Histochemie. BirkhäuserGoogle Scholar
  65. Miescher F (1897) Die histochemischen und physiologischen Arbeiten von Friedrich Miescher. VogelGoogle Scholar
  66. Misteli T (2001) The concept of self-organization in cellular architecture. J Cell Biol 155(2):181–186CrossRefPubMedPubMedCentralGoogle Scholar
  67. Monneron A, Bernhard W (1969) Fine structural organization of the interphase nucleus in some mammalian cells. J Ultrastruct Res 27(3):266–288Google Scholar
  68. Naumova N, Imakaev M, Fudenberg G, Zhan Y, Lajoie BR, Mirny LA, Dekker J. Organization of the mitotic chromosome. Science 342(6161):948–953Google Scholar
  69. Olins DE, Olins AL (2003) Chromatin history: our view from the bridge. Nat Rev Mol Cell Biol 4(10):809–814Google Scholar
  70. Osborne CS, Chakalova L, Brown KE, Carter D, Horton A, Debrand E, Goyenechea B, Mitchell JA, Lopes S, Reik W et al (2004) Active genes dynamically colocalize to shared sites of ongoing transcription. Nature Genet 36(10):1065–1071Google Scholar
  71. Ozer G, Luque A, Schlick T (2015) The chromatin fiber: multiscale problems and approaches. Current Opin Struct Biol 31:124–139Google Scholar
  72. Pauling L, Corey RB (1953) A proposed structure for the nucleic acids. Proc Natl Academy Sci 39(2):84–97Google Scholar
  73. Pauling L, Corey RB, Branson HR (1951) The structure of proteins: two hydrogen-bonded helical configurations of the polypeptide chain. Proc Natl Academy Sci 37(4):205–211Google Scholar
  74. Pollister AW (1952) Nucleoproteins of the nucleus. Exp Cell Res Suppl II 59–74Google Scholar
  75. Porter KR, Claude A, Fullam EF (1945) A study of tissue culture cells by electron microscopy methods and preliminary observations. J Exp Med 81(3):233–246Google Scholar
  76. Prakash K, Fournier D, Redl S, Best G, Borsos M, Tiwari VK, Tachibana-Konwalski K, Ketting RF, Parekh SH, Cremer C et al (2015) Superresolution imaging reveals structurally distinct periodic patterns of chromatin along pachytene chromosomes. Proc Natl Academy Sci 112(47):14635–14640Google Scholar
  77. Prasher DC, Eckenrode VK, Ward WW, Prendergast FG, Cormier MJ (1992) Primary structure of the aequorea victoria green-fluorescent protein. Gene 111(2):229–233Google Scholar
  78. Purkyně JE (1830) Symbolae ad ovi avium historiam ante incubationemGoogle Scholar
  79. Rajapakse I, Groudine M (2011) On emerging nuclear order. J Cell Biol 192(5):711–721CrossRefPubMedPubMedCentralGoogle Scholar
  80. Rao SSP, Huntley MH, Durand NC, Stamenova EK, Bochkov ID, Robinson JT, Sanborn AL, Machol I, Omer AD, Lander ES et al (2014) A 3d map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159(7):1665–1680Google Scholar
  81. Reymann J, Baddeley D, Gunkel M, Lemmer P, Stadter W, Jegou T, Rippe K, Cremer C, Birk U (2008) High-precision structural analysis of subnuclear complexes in fixed and live cells via spatially modulated illumination (smi) microscopy. Chromosome Research 16(3):367–382CrossRefPubMedGoogle Scholar
  82. Rust MJ, Bates M, Zhuang X (2006) Stochastic optical reconstruction microscopy (storm) provides sub-diffraction-limit image resolution. Nature Methods 3(10):793Google Scholar
  83. Sanborn AL, Rao SSP, Huang S-C, Durand NC, Huntley MH, Jewett AI, Bochkov ID, Chinnappan D, Cutkosky Ak, Li J et al (2015) Chromatin extrusion explains key features of loop and domain formation in wild-type and engineered genomes. Proc Natl Academy Sci 201518552Google Scholar
  84. Sanger F(1981) Determination of nucleotide sequences in dna. Biosci Report 1(1):3–18Google Scholar
  85. Schardin M, Cremer T, Hager HD, Lang M (1985) Specific staining of human chromosomes in chinese hamster x man hybrid cell lines demonstrates interphase chromosome territories. Hum Genet 71(4):281–287Google Scholar
  86. Schrödinger E (1945) What is lifeGoogle Scholar
  87. Shachar S, Voss TyC, Pegoraro G, Sciascia N, Misteli T (2015) Identification of gene positioning factors using high-throughput imaging mapping. Cell 162(4):911–923Google Scholar
  88. Shilatifard A (2006) Chromatin modifications by methylation and ubiquitination: implications in the regulation of gene expression. Annu Rev Biochem 75:243–269Google Scholar
  89. Smeets D, Markaki Y, Schmid VJ, Kraus F, Tattermusch A, Cerase A, Sterr M, Fiedler S, Demmerle J, Popken J, et al. Three-dimensional super-resolution microscopy of the inactive x chromosome territory reveals a collapse of its active nuclear compartment harboring distinct xist rna foci. Epigenet & Chromatin 7 (8), 2014Google Scholar
  90. Smith KC (1962) Dose dependent decrease in extractability of dna from bacteria following irradiation with ultraviolet light or with visible light plus dye. Biochem Biophys Res Commun 8(3):157–163Google Scholar
  91. Spilianakis CG, Lalioti MD, Town T, Lee GR, Flavell RA (2005) Interchromosomal associations between alternatively expressed loci. Nature 435(7042):637–645Google Scholar
  92. Stack SM, Brown DB, Dewey WC (1977) Visualization of interphase chromosomes. J Cell Sci 26(1):281–299Google Scholar
  93. Stedman E, Stedman E (1951) The basic proteins of cell nuclei. Philos Trans Royal Soc London B Biol Sci 235(630):565–595Google Scholar
  94. Strutevant A (1913) The linear arrangement of six sex-linked factors indrosophila as shown by their mode of association. Mol Gen Genet MGG 10(1):293–294Google Scholar
  95. Sutherland H, Bickmore WA (2009) Transcription factories: gene expression in unions?. Nature Rev Genet 10(7):457–466Google Scholar
  96. Uhlmann F (2014) A silent revolution in chromosome biology. Nature Rev Mol Cell Biol 15(7):431–431Google Scholar
  97. Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA et al (2001) The sequence of the human genome. Science 291(5507):1304–1351Google Scholar
  98. Watson J (2012) The double helix. Hachette, UKGoogle Scholar
  99. Watson JD (1963) Involvement of rna in the synthesis of proteins. Science 140(3562):17–26Google Scholar
  100. Watson JD, Crick FHC et al (1953) Molecular structure of nucleic acids. Nature 171(4356):737–738Google Scholar
  101. Weismann A (1892) Das Keimplasma; eine Theorie der Vererbung. FischerGoogle Scholar
  102. Zinner R, Teller K, Versteeg R, Cremer T, Cremer M (2007) Biochemistry meets nuclear architecture: multicolor immuno-fish for co-localization analysis of chromosome segments and differentially expressed gene loci with various histone methylations. Advances Enzyme Regul 47(1):223–241CrossRefGoogle Scholar
  103. Żurek-Biesiada D, Szczurek AT, Prakash K, Mohana GK, Lee H-K, Roignant J-Y, Birk U, Dobrucki JW, Cremer C (2015) Localization microscopy of DNA in situ using vybrant dyecycle violet fluorescent probe: A new approach to study nuclear nanostructure at single molecule resolution. Exp Cell ResGoogle Scholar

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© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Heidelberg UniversityHeidelbergGermany
  2. 2.Institute of Molecular Biology (IMB)MainzGermany

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