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|Title:||Biophysical studies of chromatin folding and unfolding|
|Doctoral Committee Chair(s):||Widom, Jonathan|
|Department / Program:||Chemistry|
|Degree Granting Institution:||University of Illinois at Urbana-Champaign|
|Abstract:||Chromatin, the building material of chromosomes, is folded and unfolded by several levels, providing a physical basis of coordinated DNA functions in eukaryotic cells. Chromatin folding is started with a linear long string of nucleosomes, connected by segments of DNA called linker DNA. Further folding forms the higher order structure, 30-nm fibers in which form most DNA in interphase nuclei is maintained. Nucleosomes arrange helically at this level, but the connectivity of the nucleosomes is unclear, and depends on the structure of linker DNA.
Hydrodynamic and electron microscopic studies were carried out on short defined-length oligomers of chromatin, dinucleosomes, to investigate the structure of linker DNA and its relationship with chromatin folding and unfolding. It is found that ionic conditions that stabilize the folding of long chromatin cause linker DNA to bend, bringing the two nucleosomes into contact. The results uphold a key prediction of the solenoid model of chromatin folding. The role of H1 (and its variant H5) is further tested in the process of linker DNA bending and chromatin folding. It is found that dinucleosomes from which the H1 and H5 have been removed are able to compact to the same extent as native dinucleosomes. The transition is shifted to higher salt concentrations. Therefore, H1 is not essential for compacting the chromatin filament, but contributes to the free energy of compaction. It is suggested that H1 may select a single, ordered and compact state (the 30-nm filaments) from a family of compact states which are possible in its absence. Finally, the unfolding of chromatin induced by the torsional stress in chromatin DNA is studied in the context of the interaction of DNA binding drugs with chromatin. It is found that DNA binding drugs that change the twist of DNA can disrupt the specific interaction between core DNA and core histones, and the nucleosome to nucleosome contact across a single linker, thereby extending linker DNA and unfolding chromatin. The results suggest a new mechanism to unfold chromatin.
|Rights Information:||Copyright 1991 Yao, Jian|
|Date Available in IDEALS:||2011-05-07|
|Identifier in Online Catalog:||AAI9211048|