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dc.contributor.advisorBotchkarev, Vladimir A.
dc.contributor.advisorMardaryev, Andrei N.
dc.contributor.advisorFessing, Michael Y.
dc.contributor.authorMalashchuk, Igor
dc.date.accessioned2018-02-01T16:38:16Z
dc.date.available2018-02-01T16:38:16Z
dc.date.issued2018-02-01
dc.identifier.urihttp://hdl.handle.net/10454/14791
dc.description.abstractEpigenetic regulatory mechanisms play important roles in the control of lineage-specific differentiation during development. However, mechanisms that regulate higher-order chromatin remodelling and transcription of keratinocyte-specific genes that are clustered in the genome into three distinct loci (Keratin type I/II loci and Epidermal Differentiation Complex (EDC) during differentiation of the epidermis are poorly understood. By using 3D-Fluorescent In Situ Hybridization (FISH), we determined that in the epidermal keratinocytes, the KtyII and EDC loci are located closely to each other in the nuclear compartment enriched by the nuclear speckles. However, in KtyII locus knockout mice, EDC locus moved away from the KtyII locus flanking regions and nuclear speckles towards the nuclear periphery, which is associated with marked changes in gene expression described previously. Chromatin architectural protein Ctcf has previously been implicated in the control of long-range enhancer-promoter contacts and inter-chromosomal interactions. Ctcf is broadly expressed in the skin including epidermal keratinocytes and hair follicles. Conditional Keratin 14-driven Ctcf ablation in mice results in the increase of the epidermal thickness, proliferation, alterations of the epidermal barrier and the development of epidermal pro-inflammatory response. Epidermal barrier defects in Krt14CreER/Ctcf fl/fl mice are associated with marked changes in gene expression in the EDC and KtyII loci, which become topologically segregated in the nucleus upon Ctcf ablation. Therefore, these data suggest that Ctcf serves as critical determinant regulating higher-order chromatin organization in lineage-specific gene loci in epidermal keratinocytes, which is required for the proper control of gene expression, maintenance of the epidermal barrier and its function.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>.eng
dc.subjectThree dimensional genome organisation; Skin; Ctcf (Chromatin architectural protein); Microarray; Fluorescent in situ hybridization; Epigenetic regulation; Epidermal barrieren_US
dc.titleEpigenetic Regulation of Skin Development and Postnatal Homeostasis The role of chromatin architectural protein Ctcf in the control of Keratinocyte Differentiation and Epidermal Barrier Formationen_US
dc.type.qualificationleveldoctoralen_US
dc.publisher.institutionUniversity of Bradfordeng
dc.publisher.departmentSchool of Medical Sciencesen_US
dc.typeThesiseng
dc.type.qualificationnamePhDen_US
dc.date.awarded2016
refterms.dateFOA2018-07-29T03:52:51Z


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