Chromatin Organization and Gene Regulation in Granulocytic Cells

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dc.contributor.advisor O'Sullivan, J en
dc.contributor.advisor Perry, J en
dc.contributor.advisor Vickers, M en Jacobson, Elsie en 2019-07-30T03:10:16Z en 2018 en
dc.identifier.uri en
dc.description.abstract Cells in the human body are exposed to a wide range of stimuli, often simultaneously. In order to survive, cells must mount cell-type-, context-, and stimuli-specific responses, which can be modulated by genetic variation. The nucleus plays an important role in integrating these extracellular signals, and producing the appropriate cellular changes. In this thesis I investigate chromatin and transcriptional changes that occur in an acute myeloid leukemia cell line (HL-60/S4) after treatment with mechanical and chemical stimuli. I migrated neutrophil-like cells through a confined space to test the effects of mechanical stimulus on the nucleus. I found that cellular remodeling is associated with disruption to the organization of silent chromatin, while transcriptional programs seem largely undisturbed by migration with constriction. Treatment of undifferentiated and neutrophil-like cells with the proinflammatory cytokine TNF-a identified cell-type-specific responses to chemical stimulus. Divergent transcriptional responses were identified in the two cell types, characterized by upregulation of cell cycle genes in undifferentiated cells, and repression of the same genes in neutrophil-like cells. Comparisons to publicly available data characterized the genome structures of two versions of the HL-60 cell line, to gain insight into the reproducibility of experiments performed in this cell line. Multiple samples of HL-60/S4 have highly consistent genomic architectures. However, different sources of the original HL-60 cell line have a small number of disparities in their cytogenetic information. In conclusion, a crucial role of nuclear architecture is to enhance the response to critical stimuli, while minimizing the response to irrelevant signals. en
dc.publisher ResearchSpace@Auckland en
dc.relation.ispartof PhD Thesis - University of Auckland en
dc.relation.isreferencedby UoA99265190804302091 en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
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dc.rights.uri en
dc.title Chromatin Organization and Gene Regulation in Granulocytic Cells en
dc.type Thesis en Biomedical Science en The University of Auckland en Doctoral en PhD en
dc.rights.holder Copyright: The author en
dc.rights.accessrights en
pubs.elements-id 777414 en Liggins Institute en
pubs.record-created-at-source-date 2019-07-30 en

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