Edinburgh Research Archive

Using native nucleosome arrays to study OCT4 and SOX2 pioneer activity

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dc.contributor.advisor
Rosser, Susan
dc.contributor.advisor
Soufi, Abdenour
dc.contributor.author
Furlong, Katharine
dc.date.accessioned
2023-05-15T09:35:51Z
dc.date.available
2023-05-15T09:35:51Z
dc.date.issued
2023-05-15
dc.description.abstract
Cell identity is the control of gene transcription by Transcription Factors (TF) and chromatin. The extent to which human cell identity can be recapitulated outside of the cell using TFs and nucleosomes in unknown. I investigate if hESC-like nucleosome positioning, MNase-sensitivity and OCT4 and SOX2 (OS) binding can be recapitulated in vitro. Nucleosomes reconstitute well into cell-like positions upon human DNA sequences in vitro as determined by MNase-seq. These in vitro nucleosomes display fragility, but these nucleosomes are not fragile in hESCs. A sub-population of 110bp nucleosomes are reconstituted, which demonstrate similar MNase-resistance as the 150bp population of nucleosomes. The addition of OS to the reconstituted nucleosomes reveals SOX2-lead binding to MNase-sensitive 110bp nucleosomes, recapitulating OS binding to MNase-sensitive nucleosomes in hESCs. However, binding locations and hESC motifs are not recapitulated in vitro. These results contribute to the understanding of human nucleosome properties, and pioneer factor targeting of chromatin.
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dc.identifier.uri
https://hdl.handle.net/1842/40561
dc.identifier.uri
http://dx.doi.org/10.7488/era/3326
dc.language.iso
en
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dc.publisher
The University of Edinburgh
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dc.subject
nucleosome arrays
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dc.subject
OCT4
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dc.subject
SOX2
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dc.subject
Cell identity
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dc.subject
gene transcription
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dc.subject
Transcription Factors
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dc.subject
chromatin
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dc.subject
human cell identity
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dc.subject
nucleosomes
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dc.subject
hESC-like nucleosome positioning
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dc.subject
MNase-sensitivity
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dc.subject
MNase-resistance
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dc.subject
MNase-sensitive nucleosomes
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dc.title
Using native nucleosome arrays to study OCT4 and SOX2 pioneer activity
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dc.type
Thesis or Dissertation
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dc.type.qualificationlevel
Doctoral
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dc.type.qualificationname
PhD Doctor of Philosophy
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Biological Sciences thesis and dissertation collection