The overall objective of this research is to contribute to understanding of the structure and dynamics of chromatin--in particular, how that structure can change in response to the stresses involved in processes like transcription and replication. A body of knowledge fundamental to such understanding is data on the thermodynamic stability of the nucleosome, the unitary element of chromatin structure. Such information will be sought through physical studies of reconstituted systems, using cloned DNA molecules carrying """"""""positioning"""""""" sequences and purified histone oligomers. The association-dissociation equilibria of DNA with the (H3-H4)2 tetramer will be first studied, followed by analysis of the reaction of the complex so formed with (H2A-H2B) dimers. Comparative stability studies will examine the effects of different regions in the DNA sequence on stability. Finally, a series of experiments utilizing different topological forms of a very small """"""""minichromosome"""""""" (containing three nucleosome sites) will be directed toward an analysis of the quantitative effects of superhelical tension on nucleosome stability.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Molecular Cytology Study Section (CTY)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Oregon State University
Schools of Arts and Sciences
United States
Zip Code
Robert, C H (1995) Estimating friction coefficients of mixed globular/chain molecules, such as protein/DNA complexes. Biophys J 69:840-8
Zlatanova, J; Leuba, S H; Yang, G et al. (1994) Linker DNA accessibility in chromatin fibers of different conformations: a reevaluation. Proc Natl Acad Sci U S A 91:5277-80
van Holde, K; Zlatanova, J (1994) Unusual DNA structures, chromatin and transcription. Bioessays 16:59-68
Varga-Weisz, P; Zlatanova, J; Leuba, S H et al. (1994) Binding of histones H1 and H5 and their globular domains to four-way junction DNA. Proc Natl Acad Sci U S A 91:3525-9
Leuba, S H; Zlatanova, J; van Holde, K (1994) On the location of linker DNA in the chromatin fiber. Studies with immobilized and soluble micrococcal nuclease. J Mol Biol 235:871-80
Miloshev, G; Venkov, P; van Holde, K et al. (1994) Low levels of exogenous histone H1 in yeast cause cell death. Proc Natl Acad Sci U S A 91:11567-70
Varga-Weisz, P; van Holde, K; Zlatanova, J (1994) Competition between linker histones and HMG1 for binding to four-way junction DNA: implications for transcription. Biochem Biophys Res Commun 203:1904-11
Leuba, S H; Yang, G; Robert, C et al. (1994) Three-dimensional structure of extended chromatin fibers as revealed by tapping-mode scanning force microscopy. Proc Natl Acad Sci U S A 91:11621-5
Leuba, S H; Zlatanova, J; 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 229:917-29
Krylov, D; Leuba, S; van Holde, K et al. (1993) Histones H1 and H5 interact preferentially with crossovers of double-helical DNA. Proc Natl Acad Sci U S A 90:5052-6

Showing the most recent 10 out of 27 publications