Topological diversity of chromatin fibers: Interplay between nucleosome repeat length, DNA linking number and the level of transcription

Davood Norouzi; Ataur Katebi; Feng Cui; Victor B. Zhurkin; Davood Norouzi; Ataur Katebi; Feng Cui; Victor B. Zhurkin

doi:10.3934/biophy.2015.4.613

AIMS Biophysics

2015, Volume 2, Issue 4: 613-629. doi: 10.3934/biophy.2015.4.613

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Topological diversity of chromatin fibers: Interplay between nucleosome repeat length, DNA linking number and the level of transcription

1.
Laboratory of Cell Biology, National Cancer Institute, NIH Bethesda, MD 20892, USA;
2.
Thomas H. Gosnell School of Life Sciences, Rochester Institute of Technology, 85 Lomb Memorial Drive, Rochester, NY 14623, USA

Received: 27 September 2015 Accepted: 28 October 2015 Published: 03 November 2015

The spatial organization of nucleosomes in 30-nm fibers remains unknown in detail. To tackle this problem, we analyzed all stereochemically possible configurations of two-start chromatin fibers with DNA linkers L = 10-70 bp (nucleosome repeat length NRL = 157-217 bp). In our model, the energy of a fiber is a sum of the elastic energy of the linker DNA, steric repulsion, electrostatics, and the H4 tail-acidic patch interaction between two stacked nucleosomes. We found two families of energetically feasible conformations of the fibers—one observed earlier, and the other novel. The fibers from the two families are characterized by different DNA linking numbers—that is, they are topologically different. Remarkably, the optimal geometry of a fiber and its topology depend on the linker length: the fibers with linkers L = 10n and 10n + 5 bp have DNA linking numbers per nucleosome DLk >>-1.5 and -1.0, respectively. In other words, the level of DNA supercoiling is directly related to the length of the inter-nucleosome linker in the chromatin fiber (and therefore, to NRL). We hypothesize that this topological polymorphism of chromatin fibers may play a role in the process of transcription, which is known to generate different levels of DNA supercoiling upstream and downstream from RNA polymerase. A genome-wide analysis of the NRL distribution in active and silent yeast genes yielded results consistent with this assumption.
- chromatin fiber,
- nucleosome repeat length,
- DNA linking number,
- DNA topology,
- regulation of transcription
Citation: Davood Norouzi, Ataur Katebi, Feng Cui, Victor B. Zhurkin. Topological diversity of chromatin fibers: Interplay between nucleosome repeat length, DNA linking number and the level of transcription[J]. AIMS Biophysics, 2015, 2(4): 613-629. doi: 10.3934/biophy.2015.4.613

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Abstract

The spatial organization of nucleosomes in 30-nm fibers remains unknown in detail. To tackle this problem, we analyzed all stereochemically possible configurations of two-start chromatin fibers with DNA linkers L = 10-70 bp (nucleosome repeat length NRL = 157-217 bp). In our model, the energy of a fiber is a sum of the elastic energy of the linker DNA, steric repulsion, electrostatics, and the H4 tail-acidic patch interaction between two stacked nucleosomes. We found two families of energetically feasible conformations of the fibers—one observed earlier, and the other novel. The fibers from the two families are characterized by different DNA linking numbers—that is, they are topologically different. Remarkably, the optimal geometry of a fiber and its topology depend on the linker length: the fibers with linkers L = 10n and 10n + 5 bp have DNA linking numbers per nucleosome DLk >>-1.5 and -1.0, respectively. In other words, the level of DNA supercoiling is directly related to the length of the inter-nucleosome linker in the chromatin fiber (and therefore, to NRL). We hypothesize that this topological polymorphism of chromatin fibers may play a role in the process of transcription, which is known to generate different levels of DNA supercoiling upstream and downstream from RNA polymerase. A genome-wide analysis of the NRL distribution in active and silent yeast genes yielded results consistent with this assumption.

References

[1]	van Holde K, Zlatanova J (2007) Chromatin fiber structure: Where is the problem now? Semin Cell Dev Biol 18: 651-658. doi: 10.1016/j.semcdb.2007.08.005
[2]	Tremethick DJ (2007) Higher-order structures of chromatin: the elusive 30 nm fiber. Cell 128: 651-654. doi: 10.1016/j.cell.2007.02.008
[3]	Schlick T, Hayes J, Grigoryev S (2012) Toward convergence of experimental studies and theoretical modeling of the chromatin fiber. J Biol Chem 287: 5183-5191. doi: 10.1074/jbc.R111.305763
[4]	Luger K, Dechassa ML, Tremethick DJ (2012) New insights into nucleosome and chromatin structure an ordered state or a disordered affair? Nat Rev Mol Cell Biol 13: 436-447. doi: 10.1038/nrm3382
[5]	Davey CA, Sargent DF, Luger K, et al. (2002) Solvent mediated interactions in the structure of the nucleosome core particle at 1.9 Å resolution. J Mol Biol 319: 1097-1113.
[6]	Dorigo B, Schalch T, Kulangara A, et al. (2004) Nucleosome arrays reveal the two-start organization of the chromatin fiber. Science 306: 1571-1573. doi: 10.1126/science.1103124
[7]	Schalch T, Duda S, Sargent DF, et al. (2005) X-ray structure of a tetra-nucleosome and its implications for the chromatin fiber. Nature 436: 138-141. doi: 10.1038/nature03686
[8]	Song F, Chen P, Sun D, et al. (2014) Cryo-EM study of the chromatin fiber reveals a double helix twisted by tetranucleosomal units. Science 344: 376-380. doi: 10.1126/science.1251413
[9]	Routh A, Sandin S, Rhodes D (2008) Nucleosome repeat length and linker histone stoichiometry determine chromatin fiber structure. Proc Natl Acad Sci U S A 105: 8872-8877. doi: 10.1073/pnas.0802336105
[10]	Robinson PJJ, Fairall L, Huynh VAT, et al. (2006) EM measurements define the dimensions of the “30-nm” chromatin fiber: evidence for a compact, interdigitated structure. Proc Natl Acad Sci U S A 103: 6506-6511.
[11]	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: 19-42. doi: 10.1006/jmbi.1997.1494
[12]	Lohr DE (1981) Detailed analysis of the nucleosomal organization of transcribed DNA in yeast chromatin. Biochemistry, 20: 5966-5972. doi: 10.1021/bi00524a007
[13]	Strauss F, Prunell A (1983) Organization of internucleosomal DNA in rat liver chromatin. EMBO J 2: 51-56.
[14]	Wang J, Fondufe-Mittendorf Y, Xi L, et al. (2008) Preferentially quantized linker DNA lengths in Saccharomyces cerevisiae. PLoS Comput Biol 4: e1000175. doi: 10.1371/journal.pcbi.1000175
[15]	Cui F, Cole HA, Clark DJ, et al. (2012) Transcriptional activation of yeast genes disrupts intragenic nucleosome phasing. Nucleic Acids Res 40: 10753-10764. doi: 10.1093/nar/gks870
[16]	Correll SJ, Schubert MH, Grigoryev SA (2012) Short nucleosome repeats impose rotational modulations on chromatin fibre folding. EMBO J 31: 2416-2426. doi: 10.1038/emboj.2012.80
[17]	Worcel A, Strogatz S, Riley D (1981) Structure of chromatin and the linking number of DNA. Proc Natl Acad Sci U S A 78: 1461-1465. doi: 10.1073/pnas.78.3.1461
[18]	Woodcock CL, Frado LL, Rattner JB (1984) The higher-order structure of chromatin: evidence for a helical ribbon arrangement. J Cell Biol 99: 42-52. doi: 10.1083/jcb.99.1.42
[19]	Williams SP, Athey BD, Muglia LJ, et al. (1986) Chromatin fibers are left-handed double helices with diameter and mass per unit length that depend on linker length. Biophys J 49: 233-248. doi: 10.1016/S0006-3495(86)83637-2
[20]	Fogg JM, Randall GL, Pettitt BM, et al. (2012) Bullied no more: when and how DNA shoves proteins around. Q Rev Biophys 45: 257-299. doi: 10.1017/S0033583512000054
[21]	Baranello L, Levens D, Gupta A, et al. (2012) The importance of being supercoiled: how DNA mechanics regulate dynamic processes. Biochim Biophys Acta 1819: 632-638. doi: 10.1016/j.bbagrm.2011.12.007
[22]	Koslover EF, Fuller CJ, Straight AF, et al. (2010) Local geometry and elasticity in compact chromatin structure. Biophys J 99: 3941-3950. doi: 10.1016/j.bpj.2010.10.024
[23]	Scipioni A, Turchetti G, Morosetti S, et al. (2010) Geometrical, conformational and topological restraints in regular nucleosome compaction in chromatin. Biophys Chem 148: 56-67. doi: 10.1016/j.bpc.2010.02.010
[24]	Norouzi D, Zhurkin VB (2015) Topological polymorphism of the two-start chromatin fiber. Biophys J 108: 2591-2600. doi: 10.1016/j.bpj.2015.04.015
[25]	Germond JE, Hirt B, Oudet P, et al. (1975) Folding of the DNA double helix in chromatin-like structures from simian virus 40. Proc Natl Acad Sci U S A 72: 1843-1847. doi: 10.1073/pnas.72.5.1843
[26]	Simpson RT, Thoma F, Brubaker JM (1985) Chromatin reconstituted from tandemly repeated cloned DNA fragments and core histones: a model system for study of higher order structure. Cell 42: 799-808. doi: 10.1016/0092-8674(85)90276-4
[27]	Norton VG, Imai BS, Yau P, et al. (1989) Histone acetylation reduces nucleosome core particle linking number change. Cell 57: 449-457. doi: 10.1016/0092-8674(89)90920-3
[28]	Olson WK, Marky NL, Jernigan RL, et al. (1993) Influence of fluctuations on DNA curvature A comparison of flexible and static wedge models of intrinsically bent DNA. J Mol Biol 232: 530-554. doi: 10.1006/jmbi.1993.1409
[29]	Dickerson RE, Bansal M, Calladine CR, et al. (1989) Definitions and nomenclature of nucleic acid structure parameters. EMBO J 8: 1-4.
[30]	Olson WK, Gorin AA, Lu XJ, et al. (1998) DNA sequence-dependent deformability deduced from protein-DNA crystal complexes. Proc Natl Acad Sci U S A 95: 11163-11168. doi: 10.1073/pnas.95.19.11163
[31]	Fuller FB (1978) Decomposition of the linking number of a closed ribbon: A problem from molecular biology. Proc Natl Acad Sci U S A 75: 3557-3561. doi: 10.1073/pnas.75.8.3557
[32]	Crick FH (1976) Linking numbers and nucleosomes. Proc Natl Acad Sci U S A 73: 2639-2643. doi: 10.1073/pnas.73.8.2639
[33]	Prunell A (1998) A topological approach to nucleosome structure and dynamics: the linking number paradox and other issues. Biophys J 74: 2531-2544. doi: 10.1016/S0006-3495(98)77961-5
[34]	Levitt M (1983) Protein folding by restrained energy minimization and molecular dynamics. J Mol Biol 170: 723-764. doi: 10.1016/S0022-2836(83)80129-6
[35]	Klenin K, Langowski J (2000) Computation of writhe in modeling of supercoiled DNA. Biopolymers 54: 307-317.
[36]	Zhurkin VB, Lysov YP, Ivanov VI (1979) Anisotropic flexibility of DNA and the nucleosomal structure. Nucleic Acids Res 6: 1081-1096. doi: 10.1093/nar/6.3.1081
[37]	Ulyanov NB, Zhurkin VB (1984) Sequence-dependent anisotropic flexibility of B-DNA. A conformational study. J Biomol Struct Dyn 2: 361-385. doi: 10.1080/07391102.1984.10507573
[38]	Gorin AA, Zhurkin VB, Olson WK (1995) B-DNA twisting correlates with base pair morphology. J Mol Biol 247: 34-48. doi: 10.1006/jmbi.1994.0120
[39]	Lu X-J, Olson WK (2003) 3DNA: A software package for the analysis, rebuilding, and visualization of three-dimensional nucleic acid structures. Nucleic Acids Res 31: 5108-5121. doi: 10.1093/nar/gkg680
[40]	Lu X-J, El Hassan MA, Hunter CA (1997) Structure and Conformation of Helical Nucleic Acids: Analysis Program (SCHNAaP) J Mol Biol 273: 668-680.
[41]	Kruithof M, Chien F, Routh A, et al. (2009) Single-molecule force spectroscopy reveals a highly compliant helical folding for the 30-nm chromatin fiber. Nat Struct Mol Biol 16: 534-540. doi: 10.1038/nsmb.1590
[42]	Keller W (1975) Determination of the number of superhelical turns in simian virus 40 DNA by gel electrophoresis. Proc Natl Acad Sci U S A 72: 4876-4880. doi: 10.1073/pnas.72.12.4876
[43]	Griffith JD (1975) Chromatin structure: deduced from a minichromosome. Science 187: 1202-1203. doi: 10.1126/science.187.4182.1202
[44]	Liu LF, Wang JC (1987) Supercoiling of the DNA template during transcription. Proc Natl Acad Sci U S A 84: 7024-7027. doi: 10.1073/pnas.84.20.7024
[45]	Teves SS, Henikoff S (2014) Transcription-generated torsional stress destabilizes nucleosomes. Nat Struct Mol Biol 21: 88-94.
[46]	Cole HA, Howard BH, Clark DJ (2011) The centromeric nucleosome of budding yeast is perfectly positioned and covers the entire centromere. Proc Natl Acad Sci U S A 108: 12687-12692. doi: 10.1073/pnas.1104978108
[47]	Waern K, Snyder M (2013) Extensive transcript diversity and novel upstream open reading frame regulation in yeast. G3 (Bethesda) 3: 343-352. doi: 10.1534/g3.112.003640
[48]	Holstege FC, Jennings EG, Wyrick JJ, et al. (1998) Dissecting the regulatory circuitry of a eukaryotic genome. Cell 95: 717-728. doi: 10.1016/S0092-8674(00)81641-4
[49]	O'Sullivan JM, Tan-Wong SM, Morillon A, et al. (2004) Gene loops juxtapose promoters and terminators in yeast. Nat Genet 36: 1014-1018. doi: 10.1038/ng1411
[50]	Ansari A, Hampsey M (2005) A role for the CPF 3'-end processing machinery in RNAP II dependent gene looping. Genes Dev 19: 2969-2978. doi: 10.1101/gad.1362305
[51]	Cole HA, Howard BH, Clark DJ (2011) Activation-induced disruption of nucleosome position clusters on the coding regions of Gcn4-dependent genes extends into neighbouring genes. Nucleic Acids Res 39: 9521-9535. doi: 10.1093/nar/gkr643
[52]	Hsieh TS, Weiner A, Lajoie B, et al. (2015) Mapping Nucleosome Resolution Chromosome Folding in Yeast by Micro-C. Cell 162: 108-119. doi: 10.1016/j.cell.2015.05.048
[53]	Teif VB, Vainshtein Y, Caudron-Herger M, et al. (2012) Genome-wide nucleosome positioning during embryonic stem cell development. Nat Struct Mol Biol 19: 1185-1192. doi: 10.1038/nsmb.2419
[54]	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: 17-25. doi: 10.1007/s10577-005-1024-3
[55]	Beshnova DA, Cherstvy AG, Vainshtein Y, et al. (2014) Regulation of the nucleosome repeat length in vivo by the DNA sequence, protein concentrations and long-range interactions. PLoS Comput Biol 10: e1003698. doi: 10.1371/journal.pcbi.1003698
[56]	Cherstvy AG, Teif VB (2014) Electrostatic effect of H1-histone protein binding on nucleosome repeat length. Phys Biol 11: 044001. doi: 10.1088/1478-3975/11/4/044001
[57]	Kireeva ML, Walter W, Tchernajenko V, et al. (2002) Nucleosome remodeling induced by RNA polymerase II: loss of the H2A/H2B dimer during transcription. Mol Cell 9: 541-552. doi: 10.1016/S1097-2765(02)00472-0
[58]	Zlatanova J, Victor J (2009) How are nucleosomes disrupted during transcription elongation?. HFSP J 3: 373-378. doi: 10.2976/1.3249971
[59]	Becavin C, Barbi M, Victor J, et al. (2010) Transcription within condensed chromatin: Steric hindrance facilitates elongation. Biophys J 98: 824-833. doi: 10.1016/j.bpj.2009.10.054
[60]	Teves SS, Henikoff S (2014) DNA torsion as a feedback mediator of transcription and chromatin dynamics. Nucleus 5: 211-218. doi: 10.4161/nucl.29086
[61]	Bi X, Broach JR (1997) DNA in transcriptionally silent chromatin assumes a distinct topology that is sensitive to cell cycle progression. Mol Cell Bio 17: 7077-7087. doi: 10.1128/MCB.17.12.7077
[62]	Tolstorukov MY, Colasanti AV, McCandlish DM, et al. (2007) A novel roll-and-slide mechanism of DNA folding in chromatin: implications for nucleosome positioning. J Mol Biol 371: 725-738. doi: 10.1016/j.jmb.2007.05.048
[63]	Humphrey W, Dalke A, Schulten K (1996) VMD, Visual molecular dynamics. J Mol Graph 14: 33-8, 27-8. doi: 10.1016/0263-7855(96)00018-5
[64]	Venters BJ, Pugh BF (2009) How eukaryotic genes are transcribed. Crit Rev Biochem Mol Biol 44: 117-141.

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