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dc.contributor.advisorBotchkarev, Vladimir A.
dc.contributor.advisorFessing, Michael Y.
dc.contributor.authorGdula, Michal R.*
dc.date.accessioned2012-02-13T17:11:37Z
dc.date.available2012-02-13T17:11:37Z
dc.date.issued2012-02-13
dc.identifier.urihttp://hdl.handle.net/10454/5382
dc.description.abstractDuring development, multipotent stem cells establish tissue-specific programmes of gene expression that underlie a process of differentiation into specialized cell types. It was shown in the study that changes in the nuclear architecture during terminal keratinocyte differentiation show correlation with the dynamics of the transcriptional and metabolic activity. In particular, terminal differentiation is accompanied by the decrease of nuclear volume, elongation of its shape, reduction of the number and fusion of nucleoli, increase in the number of centromeric clusters and a dramatic decrease of the transcriptional activity. Global changes in the nuclear architecture of epidermal keratinocytes are associated with marked remodelling of the higher-order chromatin structure of the epidermal differentiating complex (EDC). EDC is positioned peripherally in the epidermal nuclei at E11.5 when its genes show low expression levels and relocates towards the nuclear interior at E16.5 when EDC genes are markedly upregulated. P63 transcription factor serving as a master regulator of epidermal development is involved in the control of EDC relocation in epidermal progenitor cells. The epidermis of E16.5 p63KO exhibits significantly more peripheral positioning of the EDC loci, compared to wild-type. The genome organizer Satb1 serving as a direct p63 target controls higher order chromatin folding of the central part of EDC and Satb1 knockout mice show alterations of epidermal development and expression of the EDC encoded genes. Thus, this study shows that the programme of epidermal development and terminal differentiation is regulated by p63 and other factors and include marked remodelling of three-dimensional nuclear organization and positioning of tissue specific gene loci. In addition to the direct involvement of p63 in controlling the expression of tissue-specific genes, p63 via regulation of the chromatin remodelling factors such as Satb1 promotes establishing specific conformation of the EDC locus required for efficient expression of terminal differentiation-associated genes.en_US
dc.language.isoenen_US
dc.rights<a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><img alt="Creative Commons License" style="border-width:0" src="http://i.creativecommons.org/l/by-nc-nd/3.0/88x31.png" /></a><br />The University of Bradford theses are licenced under a <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/">Creative Commons Licence</a>.en_US
dc.subjectChromatin organizationen_US
dc.subject; Epidermis developmenten_US
dc.subject; Murine epidermisen_US
dc.subject; p63en_US
dc.subject; Satb1en_US
dc.subject; Multipotent stem cellsen_US
dc.subject; Keratinocyte differentiationen_US
dc.subject; Epidermal keratinocytesen_US
dc.titleEstablishing tissue-specific chromatin organization during development of the epidermis. Nuclear architecture of different layers of murine epidermis and the role of p63 and Satb1 in establishing tissue-specific organization of the epidermal differentiation complex locus.en_US
dc.type.qualificationleveldoctoralen_US
dc.publisher.institutionUniversity of Bradfordeng
dc.publisher.departmentCentre for Skin Sciences, Division of Medical Sciences, School of Life Sciencesen_US
dc.typeThesiseng
dc.type.qualificationnamePhDen_US
dc.date.awarded2011
refterms.dateFOA2018-07-19T08:58:04Z


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