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Nucleosome Fragility and Resistance: An Additional Dimension of Chromatin Structure Information in Eukaryotic Genomes

The DNA in the eukaryotic genome is wrapped in 147--bp segments around an octamer of histone proteins to form the fundamental subunit of chromatin, the nucleosome. Nucleosomes regulate
the access of proteins to DNA, thus regulating important DNA-templated events such as transcription, translation, recombination, and repair. In order to characterize the chromatin landscape
in maize, we mapped nucleosome positions using micrococcal nuclease (MNase) to enrich for nucleosomal DNA. We mapped nucleosomes under a variety of experimental conditions and in different
tissues. We identified an unexpected, nonuniform source of variation which we traced to the degree to which chromatin is digested with MNase. We exploited this property to identify
nucleosomes in the maize genome that possessed unique biochemical traits as being hypersensitive or hyper-resistant to MNase digestion. These regions were associated with important biological
processes, including gene expression levels, transcription-factor binding, and highly-conserved noncoding sequences. In addition, we found that these nucleosomes displayed tissue specificity,
implicating this special type of chromatin feature in regulating gene expression under different cell physiologies. We extended this work to the human genome and made similar discoveries:
hypersensitive nucleosomes were associated with gene expression levels and were enriched in important regulatory elements. We also found hyper-resistant nucleosomes to be highly-associated
with paused RNA polymerase II, implicating these nucleosomes in regulating transcriptional elongation. Thus, our approach to chromatin profiling uncovers novel biochemical states of
multicellular organisms that are likely important for transcription, differentiation, and cellular responses. / A Dissertation submitted to the Department of Biological Science in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Fall Semester, 2014. / November 10, 2014. / chromatin, genomics, microarrays, MNase-seq, ngs, nucleosome / Includes bibliographical references. / Hank Bass, Professor Co-Directing Dissertation; Jonathan Dennis, Professor Co-Directing Dissertation; Jinfeng Zhang, University Representative; Brian
Chadwick, Committee Member; Dave Gilbert, Committee Member.

Identiferoai:union.ndltd.org:fsu.edu/oai:fsu.digital.flvc.org:fsu_252902
ContributorsVera, Daniel (authoraut), Bass, Hank W. (professor co-directing dissertation), Dennis, Jonathan H. (Jonathan Hancock) (professor co-directing dissertation), Zhang, Jinfeng (university representative), Chadwick, Brian P. (committee member), Gilbert, David M. (committee member), Florida State University (degree granting institution), College of Arts and Sciences (degree granting college), Department of Biological Science (degree granting department)
PublisherFlorida State University, Florida State University
Source SetsFlorida State University
LanguageEnglish, English
Detected LanguageEnglish
TypeText, text
Format1 online resource (93 pages), computer, application/pdf
RightsThis Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). The copyright in theses and dissertations completed at Florida State University is held by the students who author them.

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