Advertisement

Studies of Sequence-Nonspecific HMGB DNA-Binding Proteins

  • L. James MaherIII
Chapter
Part of the Biological and Medical Physics, Biomedical Engineering book series (BIOMEDICAL)

Abstract

This chapter introduces the interesting class of eukaryotic sequence-nonspecific DNA-bending proteins known as high-mobility group B (HMGB) proteins. The general problem of DNA stiffness and compaction is first considered. Molecular characteristics of HMGB proteins and hypothetical biological roles are then reviewed. The rest of the chapter relates examples of recent work from the author and collaborators to gain mechanistic insights by ensemble and single-molecule approaches and to develop quantitative in vivo assays of DNA physical properties and the effects of HMGB proteins.

Keywords

Fluorescence Resonance Energy Transfer Optical Tweezer Persistence Length Architectural Protein HMGB Protein 
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.

Notes

Acknowledgments

The author is delighted to acknowledge the seminal contributions of present and past students (Julie Soukup, Phil Hardwidge, Andy Rodrigues, Eric Ross, Laura Cassiday, Anne Keating, Robert Dean, Joe Azok, Tessa Davis, Bob McDonald, and Justin Peters), staff scientists (Claudia McDonald, Matt Ferber, Jeff Zimmerman, and Emily Rueter) and collaborators (Jason Kahn, Michael Fried, Stephen Levine, Gerald Manning, Wilma Olson, Luke Czapla, Luis Marky, Anjum Ansari, Ivan Rasnik, Alex Vologodskii, Darrin York, Barry Gold, Rob Phillips, Yitzhak Tor, Yuan Ping Pang, Peter Privalov, Larry Parkhurst, Bill Kirk, Mark Williams, Loren Williams, Nathan Israeloff, Chris Switzer, and Udayan Mohanty). The exceptional skills and intellectual contributions of Nicole Becker are deeply appreciated. It was the teaching of Tom Record that first inspired the author’s interest in this field. Work on HMGB proteins in the author’s lab has been funded by the Mayo Foundation for Medical Education and Research and by NIH grant GM75965.

References

  1. 1.
    Garcia HG, Grayson P, Han L, Inamdar M, Kondev J, Nelson PC, Phillips R, Widom J, Wiggins PA (2007) Biological consequences of tightly bent DNA: the other life of a macromolecular celebrity. Biopolymers 85:115–130CrossRefGoogle Scholar
  2. 2.
    Shimada J, Yamakawa H (1984) Ring-closure probabilities for twisted wormlike chains. Application to DNA. Macromolecules 17:689–698CrossRefADSGoogle Scholar
  3. 3.
    Shore D, Baldwin RL (1983) Energetics of DNA twisting. I. Relation between twist and cyclization probability. J Mol Biol 170:957–981CrossRefGoogle Scholar
  4. 4.
    Shore D, Langowski J, Baldwin RL (1981) DNA flexibility studied by covalent closure of short fragments into circles. Proc Natl Acad Sci U S A 78:4833–4837CrossRefADSGoogle Scholar
  5. 5.
    Vologodskaia M, Vologodskii A (2002) Contribution of the intrinsic curvature to measured DNA persistence length. J Mol Biol 317:205–213CrossRefGoogle Scholar
  6. 6.
    Ariel G, Andelman D (2003) Persistence length of a strongly charged rodlike polyelectrolyte in the presence of salt. Phys Rev E 67:11805–11814CrossRefADSGoogle Scholar
  7. 7.
    Barrat JL, Joanny JF (1993) Persistence length of polyelectrolyte chains. Europhys Lett 24:333–338CrossRefADSGoogle Scholar
  8. 8.
    Hagerman PJ (1992) Straightening out the bends in curved DNA. Biochim Biophys Acta 1131:125–132CrossRefGoogle Scholar
  9. 9.
    Maher LJ III (1998) Mechanisms of DNA bending. Curr Opin Chem Biol 2:688–694CrossRefGoogle Scholar
  10. 10.
    Schellman JA, Harvey SC (1995) Static contributions to the persistence length of DNA and dynamic contributions to DNA curvature. Biophys Chem 55:95–114CrossRefGoogle Scholar
  11. 11.
    Williams LD, Maher LJ III (2000) Electrostatic mechanisms of DNA deformation. Annu Rev Biophys Biomol Struct 29:497–521CrossRefGoogle Scholar
  12. 12.
    Du Q, Smith C, Shiffeldrim N, Vologodskaia M, Vologodskii A (2005) Cyclization of short DNA fragments and bending fluctuations of the double helix. Proc Natl Acad Sci U S A 102:5397–5402CrossRefADSGoogle Scholar
  13. 13.
    Bellomy G, Mossing M, Record M (1988) Physical properties of DNA in vivo as probed by the length dependence of the lac operator looping process. Biochemistry 27:3900–3906CrossRefGoogle Scholar
  14. 14.
    Law SM, Bellomy GR, Schlax PJ, Record MT Jr (1993) In vivo thermodynamic analysis of repression with and without looping in lac constructs. Estimates of free and local lac repressor concentrations and of physical properties of a region of supercoiled plasmid DNA in vivo. J Mol Biol 230:161–173CrossRefGoogle Scholar
  15. 15.
    Mossing MC, Record MT Jr (1986) Upstream operators enhance repression of the lac promoter. Science 233:889–892CrossRefADSGoogle Scholar
  16. 16.
    Zhang Y, McEwen AE, Crothers DM, Levene SD (2006) Analysis of in-vivo LacR-mediated gene repression based on the mechanics of DNA looping. PLoS ONE 1:e136CrossRefADSGoogle Scholar
  17. 17.
    Travers AA, Ner SS, Churchill MEA (1994) DNA chaperones: a solution to a persistence problem. Cell 77:167–169CrossRefGoogle Scholar
  18. 18.
    Crothers DM (1993) Architectural elements in nucleoprotein complexes. Curr Biol 3:675–676CrossRefGoogle Scholar
  19. 19.
    Paull TT, Carey M, Johnson RC (1996) Yeast HMG proteins NHP6A/B potentiate promoter-specific transcriptional activation in vivo and assembly of preinitiation complexes in vitro. Genes Dev 10:2769–2781CrossRefGoogle Scholar
  20. 20.
    Paull TT, Haykinson MJ, Johnson RC (1993) The nonspecific DNA-binding and -bending proteins HMG1 and HMG2 promote the assembly of complex nucleoprotein structures. Genes Dev 7:1521–1534CrossRefGoogle Scholar
  21. 21.
    Paull TT, Johnson RC (1995) DNA looping by Saccharomyces cerevisiae high mobility group proteins NHP6A/B. J Biol Chem 270:8744–8754CrossRefGoogle Scholar
  22. 22.
    Aki T, Adhya S (1997) Repressor induced site-specific binding of HU for transcriptional regulation. EMBO J 16:3666–3674CrossRefGoogle Scholar
  23. 23.
    Lewis DE, Adhya S (2002) In vitro repression of the gal promoters by GalR and HU depends on the proper helical phasing of the two operators. J Biol Chem 277:2498–2504CrossRefGoogle Scholar
  24. 24.
    Lia G, Bensimon D, Croquette V, Allemand JF, Dunlap D, Lewis DE, Adhya S, Finzi L (2003) Supercoiling and denaturation in Gal repressor/heat unstable nucleoid protein (HU)-mediated DNA looping. Proc Natl Acad Sci U S A 100:11373–11377CrossRefADSGoogle Scholar
  25. 25.
    Thomas JO, Travers AA (2001) HMG1 and 2, and related ‘architectural’ DNA-binding proteins. Trends Biochem Sci 26:167–174CrossRefGoogle Scholar
  26. 26.
    Bianchi ME, Beltrame M (2000) Upwardly mobile proteins. Workshop: the role of HMG proteins in chromatin structure, gene expression and neoplasia. EMBO Rep 1:109–114CrossRefGoogle Scholar
  27. 27.
    Bustin M (2001) Revised nomenclature for high mobility group (HMG) chromosomal proteins. Trends Biochem Sci 26:152–153CrossRefGoogle Scholar
  28. 28.
    Grosschedl R, Giese K, Pagel J (1994) HMG domain proteins: architectural elements in the assembly of nucleoprotein structures. Trends Genet 10:94–100CrossRefGoogle Scholar
  29. 29.
    Hock R, Furusawa T, Ueda T, Bustin M (2007) HMG chromosomal proteins in development and disease. Trends Cell Biol 17:72–79CrossRefGoogle Scholar
  30. 30.
    Masse JE, Wong B, Yen YM, Allain FH, Johnson RC, Feigon J (2002) The S. cerevisiae architectural HMGB protein NHP6A complexed with DNA: DNA and protein conformational changes upon binding. J Mol Biol 323:263–284CrossRefGoogle Scholar
  31. 31.
    Swinger KK, Lemberg KM, Zhang Y, Rice PA (2003) Flexible DNA bending in HU-DNA cocrystal structures. EMBO J 22:3749–3760CrossRefGoogle Scholar
  32. 32.
    Stott K, Tang GS, Lee KB, Thomas JO (2006) Structure of a complex of tandem HMG boxes and DNA. J Mol Biol 360:90–104CrossRefGoogle Scholar
  33. 33.
    Klass J, Murphy F IV, Fouts S, Serenil M, Changela A, Siple J, Churchill ME (2003) The role of intercalating residues in chromosomal high-mobility-group protein DNA binding, bending and specificity. Nucleic Acids Res 31:2852–2864CrossRefGoogle Scholar
  34. 34.
    Ohndorf UM, Rould MA, He Q, Pabo CO, Lippard SJ (1999) Basis for recognition of cisplatin-modified DNA by high-mobility-group proteins. Nature 399:708–712CrossRefADSGoogle Scholar
  35. 35.
    Allain FH, Yen YM, Masse JE, Schultze P, Dieckmann T, Johnson RC, Feigon J (1999) Solution structure of the HMG protein NHP6A and its interaction with DNA reveals the structural determinants for non-sequence-specific binding. EMBO J 18:2563–2579CrossRefGoogle Scholar
  36. 36.
    Dragan AI, Read CM, Makeyeva EN, Milgotina EI, Churchill ME, Crane-Robinson C, Privalov PL (2004) DNA binding and bending by HMG boxes: energetic determinants of specificity. J Mol Biol 343:371–393CrossRefGoogle Scholar
  37. 37.
    Baxevanis AD, Landsman D (1995) The HMG-1 box protein family: classification and functional relationships. Nucleic Acids Res 23:1604–1613CrossRefGoogle Scholar
  38. 38.
    Bianchi ME, Beltrame M (1998) Flexing DNA: HMG-box proteins and their partners. Am J Hum Genet 63:1573–1577CrossRefGoogle Scholar
  39. 39.
    Wolffe AP (1999) Architectural regulations and Hmg1. Nat Genet 22:215–217CrossRefGoogle Scholar
  40. 40.
    Travers AA (2003) Priming the nucleosome: a role for HMGB proteins? EMBO Rep 4:131–136CrossRefGoogle Scholar
  41. 41.
    Churchill ME, Changela A, Dow LK, Krieg AJ (1999) Interactions of high mobility group box proteins with DNA and chromatin. Methods Enzymol 304:99–133CrossRefGoogle Scholar
  42. 42.
    Jung Y, Lippard SJ (2003) Nature of full-length HMGB1 binding to cisplatin-modified DNA. Biochemistry 42:2664–2671CrossRefGoogle Scholar
  43. 43.
    Becker NA, Kahn JD, Maher LJ III (2005) Bacterial repression loops require enhanced DNA flexibility. J Mol Biol 349:716–730CrossRefGoogle Scholar
  44. 44.
    Megraw TL, Chae CB (1993) Functional complementarity between the HMG1-like yeast mitochondrial histone HM and the bacterial histone-like protein HU. J Biol Chem 268:12758–12763Google Scholar
  45. 45.
    Calogero S, Grassi F, Aguzzi A, Voigtlander T, Ferrier P, Ferrari S, Bianchi ME (1999) The lack of chromosomal protein HMG1 does not disrupt cell growth but causes lethal hypoglycaemia in newborn mice. Nature Genet 22:276–280CrossRefGoogle Scholar
  46. 46.
    Kolodrubetz D, Burgum A (1990) Duplicated NHP6 genes of Saccharomyces cerevisiae encode proteins homologous to bovine high mobility group protein 1. J Biol Chem 265:3234–3239Google Scholar
  47. 47.
    Kolodrubetz D, Kruppa M, Burgum A (2001) Gene dosage affects the expression of the ­duplicated NHP6 genes of Saccharomyces cerevisiae. Gene 272:93–101CrossRefGoogle Scholar
  48. 48.
    Kruppa M, Kolodrubetz D (2001) Mutations in the yeast Nhp6 protein can differentially affect its in vivo functions. Biochem Biophys Res Commun 280:1292–1299CrossRefGoogle Scholar
  49. 49.
    Kruppa M, Moir RD, Kolodrubetz D, Willis IM (2001) Nhp6, an HMG1 protein, functions in SNR6 transcription by RNA polymerase III in S. cerevisiae. Mol Cell 7:309–318CrossRefGoogle Scholar
  50. 50.
    Aidinis V, Bonaldi T, Beltrame M, Santagata S, Bianchi ME, Spanopoulou E (1999) The RAG1 homeodomain recruits HMG1 and HMG2 to facilitate recombination signal sequence binding and to enhance the intrinsic DNA-bending activity of RAG1-RAG2. Mol Cell Biol 19:6532–6542Google Scholar
  51. 51.
    Jayaraman L, Moorthy NC, Murthy KG, Manley JL, Bustin M, Prives C (1998) High mobility group protein-1 (HMG-1) is a unique activator of p53. Genes Dev 12:462–472CrossRefGoogle Scholar
  52. 52.
    Laser H, Bongards C, Schüller J, Heck S, Johnsson N, Lehming N (2000) A new screen for protein interactions reveals that the Saccharomyces cerevisiae high mobility group proteins Nhp6A/B are involved in the regulation of the GAL1 promoter. Proc Natl Acad Sci U S A 97:13732–13737CrossRefADSGoogle Scholar
  53. 53.
    LeRoy G, Orphanides G, Lane WS, Reinberg D (1998) Requirement of RSF and FACT for transcription of chromatin templates in vitro. Science 282:1900–1904CrossRefADSGoogle Scholar
  54. 54.
    Prasad R, Liu Y, Deterding LJ, Poltoratsky VP, Kedar PS, Horton JK, Kanno S, Asagoshi K, Hou EW, Khodyreva SN, Lavrik OI, Tomer KB, Yasui A, Wilson SH (2007) HMGB1 is a cofactor in mammalian base excision repair. Mol Cell 27:829–841CrossRefGoogle Scholar
  55. 55.
    Lotze MT, Tracey KJ (2005) High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal. Nat Rev Immunol 5:331–342CrossRefGoogle Scholar
  56. 56.
    Dobi KC, Winston F (2007) Analysis of transcriptional activation at a distance in Saccharomyces cerevisiae. Mol Cell Biol 27:5575–5586CrossRefGoogle Scholar
  57. 57.
    Hershkovits G, Bangio H, Cohen R, Katcoff DJ (2006) Recruitment of mRNA cleavage/polyadenylation machinery by the yeast chromatin protein Sin1p/Spt2p. Proc Natl Acad Sci U S A 103:9808–9813CrossRefADSGoogle Scholar
  58. 58.
    Rhoades AR, Ruone S, Formosa T (2004) Structural features of nucleosomes reorganized by yeast FACT and its HMG box component, Nhp6. Mol Cell Biol 24:3907–3917CrossRefGoogle Scholar
  59. 59.
    Kamau E, Bauerle KT, Grove A (2004) The Saccharomyces cerevisiae high mobility group box protein HMO1 contains two functional DNA binding domains. J Biol Chem 279:55234–55240CrossRefGoogle Scholar
  60. 60.
    Hall DB, Wade JT, Struhl K (2006) An HMG protein, Hmo1, associates with promoters of many ribosomal protein genes and throughout the rRNA gene locus in Saccharomyces cerevisiae. Mol Cell Biol 26:3672–3679CrossRefGoogle Scholar
  61. 61.
    Merz K, Hondele M, Goetze H, Gmelch K, Stoeckl U, Griesenbeck J (2008) Actively transcribed rRNA genes in S. cerevisiae are organized in a specialized chromatin associated with the high-mobility group protein Hmo1 and are largely devoid of histone molecules. Genes Dev 22:1190–1204CrossRefGoogle Scholar
  62. 62.
    Zimmerman J, Maher LJ III (2008) Transient HMGB protein interactions with B-DNA duplexes and complexes. Biochem Biophys Res Commun 371:79–84CrossRefGoogle Scholar
  63. 63.
    Sebastian NT, Bystry EM, Becker NA, Maher LJ III (2009) Enhancement of DNA flexibility in vitro and in vivo by HMGB box A proteins carrying box B residues. Biochemistry 48:2125–2134CrossRefGoogle Scholar
  64. 64.
    McCauley M, Hardwidge PR, Maher LJ III, Williams MC (2005) Dual binding modes for an HMG domain from human HMGB2 on DNA. Biophys J 89:353–364CrossRefGoogle Scholar
  65. 65.
    Skoko D, Wong B, Johnson RC, Marko JF (2004) Micromechanical analysis of the binding of DNA-bending proteins HMGB1, NHP6A, and HU reveals their ability to form highly stable DNA-protein complexes. Biochemistry 43:13867–13874CrossRefGoogle Scholar
  66. 66.
    McCauley MJ, Zimmerman J, Maher LJ III, Williams MC (2007) HMGB binding to DNA: single and double box motifs. J Mol Biol 374:993–1004CrossRefGoogle Scholar
  67. 67.
    Zhang J, McCauley MJ, Maher LJ III, Williams MC, Israeloff NE (2009) Mechanism of DNA flexibility enhancement by HMGB proteins. Nucleic Acids Res 37:1107–1114CrossRefGoogle Scholar
  68. 68.
    Becker NA, Kahn JD, Maher LJ III (2007) Effects of nucleoid proteins on DNA repression loop formation in Escherichia coli. Nucleic Acids Res 35:3988–4000CrossRefGoogle Scholar
  69. 69.
    Kramer H, Niemoller M, Amouyal M, Revet B, von Wilcken-Bergmann B, Müller-Hill B (1987) Lac repressor forms loops with linear DNA carrying two suitably spaced lac operators. EMBO J 6:1481–1491Google Scholar
  70. 70.
    Muller J, Oehler S, Müller-Hill B (1996) Repression of lac promoter as a function of distance, phase and quality of an auxiliary lac operator. J Mol Biol 257:21–29CrossRefGoogle Scholar
  71. 71.
    Oehler S, Eismann ER, Kramer H, Müller-Hill B (1990) The three operators of the lac operon cooperate in repression. EMBO J 9:973–979Google Scholar
  72. 72.
    Zhang Y, McEwen AE, Crothers DM, Levene SD (2006) Statistical-mechanical theory of DNA looping. Biophys J 90:1903–1912CrossRefGoogle Scholar
  73. 73.
    Becker NA, Kahn JD, Maher LJ III (2008) Eukaryotic HMGB proteins as replacements for HU in E. coli repression loop formation. Nucleic Acids Res 36:4009–4021CrossRefGoogle Scholar
  74. 74.
    Bryant Z, Stone MD, Gore J, Smith SB, Cozzarelli NR, Bustamante C (2003) Structural ­transitions and elasticity from torque measurements on DNA. Nature 424:338–341CrossRefADSGoogle Scholar
  75. 75.
    Ross ED, Hardwidge PR, Maher LJ III (2001) HMG proteins and DNA flexibility in transcription activation. Mol Cell Biol 21:6598–6605CrossRefGoogle Scholar
  76. 76.
    Cloutier TE, Widom J (2004) Spontaneous sharp bending of double-stranded DNA. Mol Cell 14:355–362CrossRefGoogle Scholar
  77. 77.
    Maher LJ III (2006) DNA kinks available...if needed. Structure 14:1479–1480MathSciNetCrossRefGoogle Scholar
  78. 78.
    Ali Azam T, Iwata A, Nishimura A, Ueda S, Ishihama A (1999) Growth phase-dependent variation in protein composition of the Escherichia coli nucleoid. J Bacteriol 181:6361–6370Google Scholar
  79. 79.
    Schmid M, Durussel T, Laemmli UK (2004) ChIC and ChEC: genomic mapping of chromatin proteins. Mol Cell 16:147–157Google Scholar
  80. 80.
    Ansari A, Hampsey M (2005) A role for the CPF 3′-end processing machinery in RNAP II-dependent gene looping. Genes Dev 19:2969–2978CrossRefGoogle Scholar
  81. 81.
    Dekker J, Rippe K, Dekker M, Kleckner N (2002) Capturing chromosome conformation. Science 295:1306–1311CrossRefADSGoogle Scholar
  82. 82.
    Tang LJ, Li J, Katz DS, Feng JA (2000) Determining the DNA bending angle induced by non-specific high mobility group-1 (HMG-1) proteins: a novel method. Biochemistry 39:3052–3060CrossRefGoogle Scholar
  83. 83.
    Swinger KK, Rice PA (2004) IHF and HU: flexible architects of bent DNA. Curr Opin Struct Biol 14:28–35CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular BiologyMayo Clinic College of MedicineRochesterUSA

Personalised recommendations