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Department of Molecular Biology|College of Agriculture and Natural Resources

Dr. Jordanka Zlatanova

Department of Molecular Biology
University of Wyoming
Laramie, WY 82071
email: jordanka@uwyo.edu

Research Interests

Our laboratory is interested in chromatin structure and dynamics, and its role in transcription regulation. Chromatin is the complex between DNA and small basic proteins, histones, and consists of a repeating unit, the nucleosome, connected to linker DNA.

Fig. 1

To study chromatin structure and dynamics, we are using classical biochemical and molecular biology techniques in combination with single-molecule approaches. We have two home-built instruments that allow us to measure with high spatial and temporal resolution spontaneous and factor-induced conformational transitions in individual nucleosomal particles or single chromatin fibers. The first instrument that we call Evanescent Field Fluorescence Microscope (EFFM) allows real-time measurements of fluorescence from individual dye molecules attached to the macromolecule of interest.

Fig 2

This instrumentation allowed us to detect, for the first time, large scale, fast, spontaneous conformational transitions in the nucleosome, in which ~80 bp of DNA are unwrapping from the DNA (Tomschik et al., 2005).

Our second instrument is known as Magnetic Tweezers. In this instrument, individual DNA molecules or chromatin fibers can be manipulated via an external magnetic field acting on a magnetic bead attached to the molecule. We have used this instrument to follow the dynamics of assembly of individual chromatin fibers and its force dependence in real time (Leuba et al., 2003) and to follow in real time transcription elongation on naked DNA molecules (Pomerantz et al., 2005).

Fig 3

This research is supported by NSF grant #0504239

List of Publications

Books:

  • Tsanev, R., Russev, G., Pashev, I. and Zlatanova, J. (1992) Replication and transcription of chromatin. CRC Press, Inc., Boca Raton, Florida, 269 pg. ISBN: 0-8493-6803-0

  • Leuba, S. H. and Zlatanova, J., Eds. (2001) Biology at the single-molecule level. Pergamon, Amsterdam, etc., 251 pg. (a review of the book authored by Ishii, Y and Yanagida, T. appeared in Cell, 109, 2002, 686-688). ISBN: 0-08-044031-2.

  • Zlatanova, J., and Leuba, S. H. Eds. (2004) Chromatin structure and Dynamics: State-of-the-Art. New Comprehensive Biochemistry, vol. 39, G. Bernardi, general editor. Elsevier, Amsterdam, 507 pg. ISBN: 0-444-515941


Selected book chapters:

  • Zlatanova, J. (1992) Transcriptional regulation, eukaryotes. Encyclopedia ofMicrobiology, Lederberg, J., Ed., Academic Press, San Diego, California, v. 4, pp. 265-280

  • van Holde, K., Zlatanova, J., Arents, G. and Moudrianakis, E. (1995) Elements of chromatin structure: histones, nucleosomes, fibers. In Chromatin Structure and Gene Expression, Elgin, S. C. R., Ed., IRL Press Series "Frontiers in Molecular Biology", pp. 1-26.

  • Zlatanova, J. and Mirzabekov, A. (2000) Gel-Immobilized microarrays of nucleic acids and proteins: Production and application for macromolecular research. In DNA Arrays. Method and Protocols, Rampal, J.B., Ed., Humana Press, Totowa, NJ, pp.17-38.

  • Zlatanova, J. and Leuba, S. H. (2004) Chromatin structure and dynamics: lessons from single molecule approaches. In: Chromatin Structure and Dynamics: State-of-the-Art. Zlatanova, J. and Leuba, S. H., Eds, Elsevier, Amsterdam, pp. 309-342.

  • Zlatanova, J., Stancheva, I. and Caiafa, P. (2004) DNA methylation and chromatin structure. Ibidem.  pp. 369-396.

  • Leuba, S. H., Bennink, M. L., and Zlatanova, J. (2004) Single molecule analysis of chromatin In Chromatin and Chromatin Remodeling Enzymes, Parts A and B. Methods Enzymol. Wu, C. and C. D. Allis, C.D., Eds. 376, 73-105.

  • Bennink, M. L., Leuba, S. H. and Zlatanova, J. (2005) Analysis of protein/DNA interactions by optical tweezers: Application to chromatin fibers (by invitation). In: Protein-protein interactions: a molecular cloning manual, 2nd ed., Golemis, E. and Adams, P., Eds. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 415-425.

  • Zheng, H., Tomschik, M., Zlatanova, J. and Leuba, S. H.  (2005) Evanescent field fluorescence microscopy for analysis of protein/DNA interactions at the single-molecule level (by invitation). In: Protein-protein interactions: a molecular cloning manual, 2nd ed., Golemis, E. and Adams, P., Eds. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 429-444.


Selected publications in peer-review journals:

Review articles:

  • Zlatanova, J. (1990) Histone H1 and the transcriptional activity of eukaryotic genes. Trends Biochem. Sci. 15, 273-276.

  • Zlatanova, J. and Yaneva, J. (1991) Histone H1/DNA interactions and their relation to chromatin structure and function. DNA Cell Biol. 10, 239-248.

  • Zlatanova, J. S. and van Holde K. E. (1992) Chromatin loops and transcriptional regulation. Crit. Rev. Eukar. Gene Expr. 2, 211-224.

  • Zlatanova, J. and van Holde, K. (1992) Histone H1 and transcription - still an enigma? J. Cell Sci. 103, 889-895.

  • van Holde, K. and Zlatanova, J. (1994) Unusual DNA structures, chromatin and transcription. Bioessays 16, 59-68.

  • Zlatanova, J. and Doenecke, D. (1994) Histone H1o: a major player in cell differentiation? FASEB J. 8, 1260-1268.

  • van Holde, K. and Zlatanova, J. (1995) Chromatin higher-order structure: chasing a mirage? J. Biol. Chem. 270, 8373-8376.

  • Lohr, D., Venkov, P. and Zlatanova, J. (1995) Transcriptional regulation in the yeast GAL gene family: A complex genetic network. FASEB J. 9, 777-787.

  • Zlatanova, J. and van Holde, K. (1996) The linker histones and chromatin structure: new twists.  Prog. Nucleic Acids Res. Mol. Biol., Cohn, W. E. and Moldave, K., Eds., 52, 217-259.

  • van Holde, K. and Zlatanova, J. (1996) Chromatin architectural proteins and transcription factors:  A structural connection. BioEssays 18, 697-700.

  • van Holde, K. and Zlatanova, J. (1996) What determines the folding of the chromatin fiber? Proc. Natl. Acad. Sci. USA 93, 10548-10555.

  • Zlatanova, J. (1997) Archaeal chromatin: virtual or real? Proc. Natl. Acad. Sci. USA 94, 1251-12254.

  • Zlatanova, J., Leuba, S. H. and van Holde, K. (1998) Chromatin fiber structure: morphology, molecular determinants, structural transitions. Biophys. J. 74, 2554-2566.

  • Zlatanova, J. and van Holde, K. (1998) Binding to four-way junction DNA: A common property of architectural proteins. FASEB J. 12, 421-431.

  • Zlatanova, J., Yaneva, J. and Leuba, S. H. (1998) Proteins that specifically recognize cisplatin damaged DNA: a clue to anticancer activity of cisplatin. FASEB J. 12, 791-799.

  • Zlatanova, J. and van Holde, K. (1998) Linker histones versus HMG1/2: A struggle for dominance? BioEssays 20, 584-588.

  • van Holde, K. and Zlatanova, J. (1999) The core particle: does it have structural and physiological relevance? BioEssays 21, 776-780.

  • Zlatanova, J., Leuba, S. H. and van Holde, K. (1999) Chromatin structure revisited. Crit. Rev. Eukar. Gene Expr. 9, 245-255.

  • Zlatanova, J., Caiafa, P. and van Holde, K. (2000) Linker histone binding and displacement: versatile mechanism for transcriptional regulation. FASEB J. 14, 1697-1704.

  • Zlatanova, J., Lindsay, S. M. and Leuba, S. H. (2001) Single molecule force spectroscopy in biology using the Atomic Force Microscopy. Prog. Biophys. Mol. Biol. 74, 37-61.

  • Zlatanova, J. and Leuba, S. H. (2002) Stretching and imaging single DNA molecules and chromatin. J. Muscle Res. Cell Motility, 23, 377-395.

  • Zlatanova, J. and Leuba, S. H. (2003) Magnetic tweezers: a sensitive tool to study DNA and chromatin at the single-molecule level. Biochem. Cell Biol. 81, 151-159.

  • Zlatanova, J. (2003) Forcing chromatin. J. Biol. Chem. 278, 23213-23216 (cover illustration).

  • Zlatanova, J. and Leuba, S. H. (2003) Chromatin fibers, one-at-a-time. J. Mol. Biol. 331, 1-19.

  • Zlatanova, J. (2005) MeCP2: the chromatin connection and beyond. Biochem. Cell Biol., 83, 251-262.

  • van Holde, K. and Zlatanova, J. (2006) Scanning chromatin: A new paradigm?  J. Biol. Chem.  281, 12197-12200.

  • Zlatanova, J., McAllister, W. T., Borukhov, S. and Leuba, S. H. (2006) Single-molecule approaches reveal the idiosyncrasies of RNA polymerases.   Structure 14, 953-966.

  • Zlatanova, J. and van Holde, K. (2006) Single-Molecule Biology: What is it and how does it work? (by invitation) Mol. Cell 24, 317-329.

  • Zlatanova, J., Seebart, C. and Tomschik, M. (2007) Nap1: taking a closer look at a juggler protein of extraordinary skills. FASEB J. 21, 1294-1310.

  • van Holde, K. and Zlatanova, J. (2007) Chromatin fiber structure: Where is the problem now? Seminars Cell Dev. Biol., in press.


Experimental papers:

  • Zlatanova, J. and Swetly, P. (1978) Uncoupled synthesis of histones and DNA during Friend cell differentiation. Nature 276, 276-277.

  • Zlatanova, J. (1980) Synthesis of histone H1o is not inhibited in hydroxyurea-treated Friend cells. FEBS Lett. 112, 199-202.

  • Srebreva, L., Zlatanova, J., Miloshev, G. and Tsanev, R. (1987) Immunological evidence for the existence of H1-like histone in yeast. Eur. J. Biochem. 165, 449-454.

  • Zlatanova, J., Srebreva, L., Banchev, T., Tasheva, B. and Tsanev, R. (1990) Cytoplasmic pools of histone H1 in mammalian cells. J. Cell Sci. 96, 461-468.

  • Yaneva, J. and Zlatanova, J. (1992) Histone H1 interacts specifically with certain regions of the mouse a-globin gene. DNA Cell Biol. 11, 91-99.

  • Leuba, S., Zlatanova, J. and van Holde, K. (1993) On the location of histones H1 and H5 in the chromatin fiber: studies with immobilized trypsin and chymotrypsin. J. Mol. Biol. 229, 917-929.

  • Bavykin, S., Srebreva, L., Banchev, T., Tsanev, R., Zlatanova, J. and Mirzabekov, A. (1993) Histone H1 deposition and histone-DNA interactions in replicating chromatin. Proc. Natl. Acad. Sci. USA 90, 3918-3922.

  • Krylov, D., Leuba, S., van Holde, K. and Zlatanova, J. (1993) Histones H1 and H5 interact preferentially with cross-overs of double helical DNA. Proc. Natl. Acad. Sci. USA 90, 5052-5056.

  • Varga-Weisz, P., van Holde, K. and Zlatanova, J. (1993) Preferential binding of histone H1 to four-way helical junction DNA. J. Biol. Chem. 268, 20699-20700.

  • Leuba, S., Zlatanova, J. and van Holde, K. (1994) On the location of linker DNA in the chromatin fiber. Studies with immobilized and soluble micrococcal nuclease. J. Mol. Biol. 235, 871-880.

  • Varga-Weisz, P., Zlatanova, J., Leuba, S. H., Schroth, G. P. and van Holde, K. (1994) The binding of histones H1 and H5 and their globular domains to four-way junction DNA. Proc. Natl. Acad. Sci. USA 91, 3525-3529.

  • Zlatanova, J., Leuba, S. H., Yang, G., Bustamante, C. and van Holde, K. (1994) Linker DNA accessibility in chromatin fibers of different conformations: a reevaluation. Proc. Natl. Acad. Sci. USA 91, 5277-5280.

  • Leuba, S. H., Yang, G., Robert, C., Samori, B., van Holde, K., Zlatanova, J. and Bustamante, C. (1994) Three-dimensional structure of extended chromatin fibers as revealed by tapping-mode scanning force microscopy. Proc. Natl. Acad. Sci. USA 91, 11621-11625.

  • Yang, G., Leuba, S. H., Bustamante, C., Zlatanova, J. and van Holde, K. (1994) Role of linker histones in extended chromatin fibre structure. Nature Struct. Biol. 1, 761-763.

  • Miloshev, G., Venkov, P., van Holde, K. and Zlatanova, J. (1994) Low levels of exogenous histone H1 in yeast cause cell death. Proc. Natl. Acad. Sci. USA 91, 11567-11570.

  • Yaneva, J., Schroth, G. P., van Holde, K. and Zlatanova, J. (1995) High-affinity binding sites for histone H1 in plasmid DNA. Proc. Natl. Acad. Sci. USA 92, 7060-7064.

  • Ivanchenko, M., Zlatanova, J., Varga-Weisz, P., Hassan, A. and van Holde, K. (1996) Linker histones affect patterns of digestion of supercoiled plasmids by single strand-specific nucleases. Proc. Natl. Acad. Sci. USA 93, 6970-6974.

  • Yaneva, J., Leuba, S. H., van Holde, K. and Zlatanova, J. (1997) The major chromatin protein histone H1 binds preferentially to cis-platin damaged DNA. Proc. Natl. Acad. Sci. USA 94, 13448-13451.

  • An, W., Leuba, S. H., van Holde, K. and Zlatanova, J. (1998) Linker histone protects linker DNA on only one side of the core particle and in a sequence dependent manner. Proc. Natl. Acad. Sci. USA 95, 3396-3401.

  • Leuba, S. H., Bustamante, C., Zlatanova, J. and van Holde, K. (1998) Contributions of linker histones and histone H3 to chromatin structure: SFM studies on trypsinized fibers. Biophys. J. 74, 2823-2829.

  • Leuba, S. H., Bustamante, C., van Holde, K. and Zlatanova, J. (1998) Linker histone tails and the N-tails of histone H3 are redundant: SFM studies of reconstituted fibers. Biophys. J. 74, 2830-2839.

  • An, W., van Holde, K. and Zlatanova, J. (1998) The nonhistone chromatin protein HMG1 protects linker DNA on the side opposite to that protected by linker histones. J. Biol. Chem. 273, 26289-26291.

  • Bennink, M. L., Leuba, S. H., Leno, G. H., Zlatanova, J., de Grooth B. G. and Greve, J. (2001) Unfolding individual nucleosomes by stretching single chromatin fibres with optical tweezers. Nature Struct. Biol. 8, 606-610.

  • Karymov, M. A., Tomschik, M., Leuba S. H., Caiafa, P. and Zlatanova, J. (2001) Methylation–dependent chromatin fiber compaction in vivo and in vitro: Requirement for linker histone. FASEB J. 15, 2631-2641.

  • Tomschik, M., Karymov, M. A., Zlatanova, J. and Leuba S. H. (2001) The archaeal histone-fold protein HMf organizes DNA into bona fide chromatin fibers. Structure 8, 1201-1211.

  • Leuba, S. H., Karymov, M. A., Tomschik, M., Ramjit, R., Smith, P. and Zlatanova, J. (2003) Assembly of single chromatin fiber depends on the tension in the DNA molecule: magnetic tweezers study. Proc. Natl. Acad. Sci. USA, 100, 495-500.

  • Tomschik, M., Zheng, H., van Holde K., Zlatanova, J. and Leuba, S. H. (2005) Fast, long-range, reversible conformational fluctuations in nucleosomes revealed by single-pair fluorescence resonance energy transfer. Proc. Natl. Acad. Sci. USA 102, 3278-3283.

  • Pomerantz, R. T., Ramjit, R., Gueroui, Z., Place, C., Anikin, M., Leuba, S., Zlatanova, J. and McAllister, W. T. (2005) A tightly regulated molecular motor based upon T7 RNA polymerase.  Nanoletters 5, 1698-1703.

Laboratory members

  • Miroslav (Mirek) Tomschik – senior research associate

  • Amit Thakar - postdoctoral associate

  • Satoru Fujimoto – postdoctoral associate

  • Pooja Gupta – graduate student

  • Corrine Seebart – research associate

From left to right (collective photo):  Jordanka, Pooja, Mirek, Corrine and Amit

From left to right (collective photo):  Jordanka, Pooja, Mirek, Corrine and Amit; below, Satoru

Satoru

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