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The packaging of DNA in chromatin
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Text
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Title
The packaging of DNA in chromatin
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ETD_2318
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http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.000052171
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eng
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theses
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Computational Biology and Molecular Biophysics
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(authority = ETD-LCSH)
Topic
DNA--Analysis
Subject
(ID = SBJ-3);
(authority = ETD-LCSH)
Topic
Chromatin
Abstract
The mechanical properties of DNA play a key role in its biological processing, determining how the long, thin, double-helical molecule responds to the binding of proteins and functions in confined spaces within a cell. In eukaryotes, about 75-90% of genomic DNA exists in the form of nucleosomes, which are the fundamental units of DNA packaging in chromatin and the primary determinate of DNA accessibility. The structure of chromatin undergoes various changes that depend, at least in part, upon the requirements of gene expression and other functional environments. The dynamics of DNA packaging in chromatin is thus fundamental to numerous biological processes.
The flexibility of DNA is important in packaging DNA over lengths comparable to its persistence length during genetic processing and the sequence-dependent properties of DNA determine the positioning of nucleosomes in the genome and the sites of binding of enzymes and transcription factors. In addition, understanding the correlation between DNA flexibility and histone-DNA interactions inside the nucleosome is essential for unraveling currently unsolved mechanisms of gene regulation. Furthermore, although many experimental techniques have emerged to examine the overall structure of chromatin fibers, the internal arrangement of DNA and histones remains unclear. Thus an appropriate computational model able to incorporate experimental observations is key to interpretation of the folding and unfolding of chromatin.
The major goal of this thesis is to understand some of biophysical mechanisms involved in the packaging of DNA into chromatin using computational techniques at multi-scales: (i) to determine the sequence-dependent flexibility of DNA by developing DNA deformation analysis tools and databases; (ii) to design DNA spatial configurations using knowledge-based Monte-Carlo sampling; (iii) to map protein-DNA recognition inside nucleosomes in terms of realistic molecular treatments; and (iv) to interpret the internal structure of chromatin fibers and examine chromatin looping using novel modeling and simulation methods.
The flexibility of DNA is important in packaging DNA over lengths comparable to its persistence length during genetic processing and the sequence-dependent properties of DNA determine the positioning of nucleosomes in the genome and the sites of binding of enzymes and transcription factors. In addition, understanding the correlation between DNA flexibility and histone-DNA interactions inside the nucleosome is essential for unraveling currently unsolved mechanisms of gene regulation. Furthermore, although many experimental techniques have emerged to examine the overall structure of chromatin fibers, the internal arrangement of DNA and histones remains unclear. Thus an appropriate computational model able to incorporate experimental observations is key to interpretation of the folding and unfolding of chromatin.
The major goal of this thesis is to understand some of biophysical mechanisms involved in the packaging of DNA into chromatin using computational techniques at multi-scales: (i) to determine the sequence-dependent flexibility of DNA by developing DNA deformation analysis tools and databases; (ii) to design DNA spatial configurations using knowledge-based Monte-Carlo sampling; (iii) to map protein-DNA recognition inside nucleosomes in terms of realistic molecular treatments; and (iv) to interpret the internal structure of chromatin fibers and examine chromatin looping using novel modeling and simulation methods.
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electronic resource
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xv, 191 p. : ill.
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Ph.D.
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by Guohui Zheng
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Zheng
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Guohui
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1980-
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Guohui Zheng
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Olson
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Wilma
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chair
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Advisory Committee
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Wilma K Olson
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Sengupta
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Anirvan
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Anirvan M Sengupta
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Morozov
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Alexandre
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Alexandre V Morozov
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Studitsky
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Vasily
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Vasily M Studitsky
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Rutgers University
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Graduate School - New Brunswick
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2010
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2010-01
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xx
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Rutgers University Electronic Theses and Dissertations
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Graduate School - New Brunswick Electronic Theses and Dissertations
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doi:10.7282/T398875T
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ETD doctoral
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Rights
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The author owns the copyright to this work.
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Copyright protected
Notice
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Open
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Permission or license
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Zheng
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Guohui
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2009-12-19 19:59:04
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Guohui Zheng
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Rutgers University. Graduate School - New Brunswick
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I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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