Histone Dynamics During Transcription: Exchange of H2A/H2B Dimers and H3/H4 Tetramers During Pol II Elongation

  • Christophe Thiriet
  • Jeffrey J. HayesEmail author
Part of the Results and Problems in Cell Differentiation book series (RESULTS, volume 41)


Chromatin within eukaryotic cell nuclei accommodates many complex activities that require at least partial disassembly and reassembly of nucleosomes. This disassembly/reassembly is thought to be somewhat localized when associated with processes such as site-specific DNA repair but likely occurs over extended regions during processive processes such as DNA replication or transcription. Here we review data addressing the effect of transcription elongation on nucleosome disassembly/reassembly, specifically focusing on the issue of transcription-dependent exchange of H2A/H2B dimers and H3/H4 tetramers. We suggest a model whereby passage of a polymerase through a nucleosome induces displacement of H2A/H2B dimers with a much higher probability than displacement of H3/H4 tetramers such that the extent of tetramer replacement is relatively low and proportional to polymerase density on any particular gene.


Histone Chaperone Histone Octamer Free Pool Hepatoma Tissue Culture Cell Histone Exchange 
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.


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This work was supported by NIH grant GM52426 and NSF grant MCB-0317935. We thank Drs. Anthony Annunziato and Vasily Studitsky for a critical reading of the manuscript.


  1. 1.
    Adkins MW, Howar SR, Tyler JK (2004) Chromatin disassembly mediated by the histone chaperone Asf1 is essential for transcriptional activation of the yeast PHO5 and PHO8 genes. Mol Cell 14:657–666 CrossRefPubMedGoogle Scholar
  2. 2.
    Ahmad K, Henikoff S (2002) The histone variant H3.3 marks active chromatin by replication-independent nucleosome assembly. Mol Cell 9:1191–1200 CrossRefPubMedGoogle Scholar
  3. 3.
    Alilat M, Sivolob A, Revet B, Prunell A (1999) Nucleosome dynamics. Protein and DNA contributions in the chiral transition of the tetrasome, the histone (H3-H4)2 tetramer-DNA particle. J Mol Biol 291:815–841 CrossRefPubMedGoogle Scholar
  4. 4.
    Allfrey VG, Faulkner R, Mirsky AE (1964) Acetylation and Methylation of Histones and Their Possible Role in the Regulation of Rna Synthesis. Proc Natl Acad Sci USA 51:786–794 PubMedCrossRefGoogle Scholar
  5. 5.
    Annunziato AA, Frado L-LY, Seale RL, Woodcock CLF (1988) Treatment with sodium butyrate inhibits the complete condensation of interphase chromatin. Chromosoma 96:132–138 CrossRefPubMedGoogle Scholar
  6. 6.
    Belotserkovskaya R, Oh S, Bondarenko VA, Orphanides G, Studitsky VM, Reinberg D (2003) FACT facilitates transcription-dependent nucleosome alteration. Science 301:1090–1093 CrossRefPubMedGoogle Scholar
  7. 7.
    Boeger H, Griesenbeck J, Strattan JS, Kornberg RD (2003) Nucleosomes unfold completely at a transcriptionally active promoter. Mol Cell 11:1587–1598 CrossRefPubMedGoogle Scholar
  8. 8.
    Boyer LA, Logie C, Bonte E, Becker PB, Wade PA, Wolffe AP, Wu C, Imbalzano AN, Peterson CL (2000) Functional delineation of three groups of the ATP-dependent family of chromatin remodeling enzymes. J Biol Chem 275:18864–18870 CrossRefPubMedGoogle Scholar
  9. 9.
    Brownell JE, Zhou J, Ranalli T, Kobayashi R, Edmondson DG, Roth SY, Allis CD (1996) Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation. Cell 84:843–851 CrossRefPubMedGoogle Scholar
  10. 10.
    Chang CH, Luse DS (1997) The H3/H4 tetramer blocks transcript elongation by RNA polymerase II in vitro. J Biol Chem 272:23427–23434 CrossRefPubMedGoogle Scholar
  11. 11.
    Clark DJ, Felsenfeld G (1992) A nucleosome core is transferred out of the path of a transcribing polymerase. Cell 71:11–22 CrossRefPubMedGoogle Scholar
  12. 12.
    Cosma MP (2002) Ordered recruitment: gene-specific mechanism of transcription activation. Mol Cell 10:227–236 CrossRefPubMedGoogle Scholar
  13. 13.
    de la Cruz X, Lois S, Sanchez-Molina S, Martinez-Balbas M (2005) Do protein motifs read the histone code? Bioessays 27:164–175 CrossRefPubMedGoogle Scholar
  14. 14.
    Felsenfeld G, Clark D, Studitsky V (2000) Transcription through nucleosomes. Biophys Chem 86:231–237 CrossRefPubMedGoogle Scholar
  15. 15.
    Giaever GN, Wang JC (1988) Supercoiling of intracellular DNA can occur in eukaryotic cells. Cell 55:849–856 CrossRefPubMedGoogle Scholar
  16. 16.
    Grunstein M (1997) Histone acetylation in chromatin structure and transcription. Nature 389:349–352 CrossRefPubMedGoogle Scholar
  17. 17.
    Hake SB, Garcia BA, Duncan EM, Kauer M, Dellaire G, Shabanowitz J, Bazett-Jones DP, Allis CD, Hunt DF (2005) Expression patterns and post-translational modifications associated with mammalian histone H3 variants. J Biol Chem Google Scholar
  18. 18.
    Hansen JC (2002) Conformational Dynamics of the Chromatin Fiber in Solution: Determinants, Mechanisms, and Functions. Annu Rev Biophys Biomol Struct 31:361–392 CrossRefPubMedGoogle Scholar
  19. 19.
    Hendzel MJ, Davie JR (1990) Nucleosomal histones of transcriptionally active/competent chromatin preferentially exchange with newly synthesized histones in quiescent chicken erythrocytes. Biochem J 271:67–73 PubMedGoogle Scholar
  20. 20.
    Huang RC, Bonner J (1962) Histone, a suppressor of chromosomal RNA synthesis. Proc Natl Acad Sci USA 48:1216–1222 PubMedCrossRefGoogle Scholar
  21. 21.
    Izban MG, Luse DS (1991) Transcription on nucleosomal templates by RNA polymerase II in vitro: inhibition of elongation with enhancement of sequence-specific pausing. Genes Dev 5:683–696 PubMedCrossRefGoogle Scholar
  22. 22.
    Jackson V, Chalkley R (1985) Histone synthesis and deposition in the G1 and S phases of hepatoma tissue culture cells. Biochemistry 24:6921–6930 CrossRefPubMedGoogle Scholar
  23. 23.
    Jackson V, Marshall S, Chalkley R (1981) The sites of deposition of newly synthesized histone. Nucleic Acids Res 9:4563–4581 PubMedCrossRefGoogle Scholar
  24. 24.
    Janicki SM, Tsukamoto T, Salghetti SE, Tansey WP, Sachidanandam R, Prasanth KV, Ried T, Shav-Tal Y, Bertrand E, Singer RH, Spector DL (2004) From silencing to gene expression: real-time analysis in single cells. Cell 116:683–698 CrossRefPubMedGoogle Scholar
  25. 25.
    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 153:1341–1353 CrossRefPubMedGoogle Scholar
  26. 26.
    Kireeva ML, Hancock B, Cremona GH, Walter W, Studitsky VM, Kashlev M (2005) Nature of the nucleosomal barrier to RNA polymerase II. Mol Cell 18:97–108 CrossRefPubMedGoogle Scholar
  27. 27.
    Kireeva ML, Walter W, Tchernajenko V, Bondarenko V, Kashlev M, Studitsky VM (2002) Nucleosome remodeling induced by RNA polymerase II: loss of the H2A/H2B dimer during transcription. Mol Cell 9:541–552 CrossRefPubMedGoogle Scholar
  28. 28.
    Knezetic JA, Luse DS (1986) The Presence of Nucleosomes on a DNA Template Prevents Initiation by RNA Polymerase II In vitro. Cell 45:95–104 CrossRefPubMedGoogle Scholar
  29. 29.
    Lee CK, Shibata Y, Rao B, Strahl BD, Lieb JD (2004) Evidence for nucleosome depletion at active regulatory regions genome-wide. Nat Genet 36:900–905 CrossRefPubMedGoogle Scholar
  30. 30.
    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 44:5357–5372 CrossRefPubMedGoogle Scholar
  31. 31.
    Louters L, Chalkley R (1985) Exchange of histones H1, H2A, and H2B in vivo. Biochemistry 24:3080–3085 CrossRefPubMedGoogle Scholar
  32. 32.
    McKittrick E, Gafken PR, Ahmad K, Henikoff S (2004) Histone H3.3 is enriched in covalent modifications associated with active chromatin. Proc Natl Acad Sci USA 101:1525–1530 CrossRefPubMedGoogle Scholar
  33. 33.
    Mito Y, Henikoff JG, Henikoff S (2005) Genome-scale profiling of histone H3.3 replacement patterns. Nat Genet 37:1090–1097 CrossRefPubMedGoogle Scholar
  34. 34.
    Orphanides G, LeRoy G, Chang CH, Luse DS, Reinberg D (1998) FACT, a factor that facilitates transcript elongation through nucleosomes. Cell 92:105–116 CrossRefPubMedGoogle Scholar
  35. 35.
    Perry CA, Dadd CA, Allis CD, Annunziato AT (1993) Analysis of nucleosome assembly and histone exchange using antibodies specific for acetylated H4. Biochemistry 32:13605–13614 CrossRefPubMedGoogle Scholar
  36. 36.
    Peterson CL (2000) ATP-dependent chromatin remodeling: going mobile. FEBS Lett 476:68–72 CrossRefPubMedGoogle Scholar
  37. 37.
    Peterson CL, Laniel MA (2004) Histones and histone modifications. Curr Biol 14:R546–R551 CrossRefPubMedGoogle Scholar
  38. 38.
    Reinke H, Horz W (2003) Histones are first hyperacetylated and then lose contact with the activated PHO5 promoter. Mol Cell 11:1599–1607 CrossRefPubMedGoogle Scholar
  39. 39.
    Sathyanarayana UG, Freeman LA, Lee MS, Garrard WT (1999) RNA polymerase-specific nucleosome disruption by transcription in vivo. J Biol Chem 274:16431–16436 CrossRefPubMedGoogle Scholar
  40. 40.
    Saunders A, Werner J, Andrulis ED, Nakayama T, Hirose S, Reinberg D, Lis JT (2003) Tracking FACT and the RNA polymerase II elongation complex through chromatin in vivo. Science 301:1094–1096 CrossRefPubMedGoogle Scholar
  41. 41.
    Schwabish MA, Struhl K (2004) Evidence for eviction and rapid deposition of histones upon transcriptional elongation by RNA polymerase II. Mol Cell Biol 24:10111–10117 CrossRefPubMedGoogle Scholar
  42. 42.
    Silverman B, Mirsky AE (1973) Accessibility of DNA in chromatin to DNA polymerase and RNA polymerase. Proc Natl Acad Sci USA 70:1326–1330 PubMedCrossRefGoogle Scholar
  43. 43.
    Strahl BD, Allis CD (2000) The language of covalent histone modifications. Nature 403:41–45 CrossRefPubMedGoogle Scholar
  44. 44.
    Studitsky VM, Clark DJ, Felsenfeld G (1994) A histone octamer can step around a transcribing polymerase without leaving the template. Cell 76:371–382 CrossRefPubMedGoogle Scholar
  45. 45.
    Studitsky VM, Clark DJ, Felsenfeld G (1995) Overcoming a nucleosomal barrier to transcription. Cell 83:19–27 CrossRefPubMedGoogle Scholar
  46. 46.
    Studitsky VM, Kassavetis GA, Geiduschek EP, Felsenfeld G (1997) Mechanism of transcription through the nucleosome by eukaryotic RNA polymerase. Science 278:1960–1963 CrossRefPubMedGoogle Scholar
  47. 47.
    Studitsky VM, Walter W, Kireeva M, Kashlev M, Felsenfeld G (2004) Chromatin remodeling by RNA polymerases. Trends Biochem Sci 29:127–135 CrossRefPubMedGoogle Scholar
  48. 48.
    Thatcher TH, MacGaffey J, Bowen J, Horowitz S, Shapiro DL, Gorovsky MA (1994) Independent evolutionary origin of histone H3.3-like variants of animals and Tetrahymena. Nucleic Acids Res 22:180–186 PubMedCrossRefGoogle Scholar
  49. 49.
    Thiriet C, Hayes JJ (2005) Replication-independent core histone dynamics at transcriptionally active loci in vivo. Genes Dev 19:677–682 CrossRefPubMedGoogle Scholar
  50. 50.
    Tsao YP, Wu HY, Liu LF (1989) Transcription-driven supercoiling of DNA: direct biochemical evidence from in vitro studies. Cell 56:111–118 CrossRefPubMedGoogle Scholar
  51. 51.
    Wirbelauer C, Bell O, Schubeler D (2005) Variant histone H3.3 is deposited at sites of nucleosomal displacement throughout transcribed genes while active histone modifications show a promoter-proximal bias. Genes Dev 19:1761–1766 CrossRefPubMedGoogle Scholar
  52. 52.
    Wolffe AP, Kurumizaka H (1998) The nucleosome: a powerful regulator of transcription. Prog Nucleic Acid Res Mol Biol 61:379–422 CrossRefGoogle Scholar
  53. 53.
    Woodcock CL, Dimitrov S (2001) Higher-order structure of chromatin and chromosomes. Curr Opin Genet Dev 11:130–135 CrossRefPubMedGoogle Scholar
  54. 54.
    Wu C (1980) The 5′ends of Drosophila heat shock genes in chromatin are hypersensitive to DNase I. Nature 286:854–860 CrossRefPubMedGoogle Scholar
  55. 55.
    Wu C, Wong YC, Elgin SC (1979) The chromatin structure of specific genes: II. Disruption of chromatin structure during gene activity. Cell 16:807–814 CrossRefPubMedGoogle Scholar
  56. 56.
    Yu L, Gorovsky MA (1997) Constitutive expression, not a particular primary sequence, is the important feature of the H3 replacement variant hv2 in Tetrahymena thermophila. Mol Cell Biol 17:6303–6310 PubMedGoogle Scholar
  57. 57.
    Zhang Y, Reinberg D (2001) Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails. Genes Dev. 15:2343–2360 CrossRefPubMedGoogle Scholar
  58. 58.
    Zheng C, Hayes JJ (2003) Structures and interactions of the core histone tail domains. Biopolymers 68:539–546 CrossRefPubMedGoogle Scholar

Authors and Affiliations

  1. 1.Department of Biochemistry and BiophysicsUniversity of Rochester Medical CenterRochesterUSA
  2. 2.Institut Andre LwoffCNRS UPR-1983Villejuif cedexFrance

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