Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM022916-19
Application #
2174003
Study Section
Molecular Cytology Study Section (CTY)
Project Start
1979-04-01
Project End
1996-03-31
Budget Start
1994-04-01
Budget End
1996-03-31
Support Year
19
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
Oregon State University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
053599908
City
Corvallis
State
OR
Country
United States
Zip Code
97339

  Publications

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

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