During 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.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/5382 |
| Date | January 2011 |
| Creators | Gdula, Michal R. |
| Contributors | Botchkarev, Vladimir A., Fessing, Michael Y. |
| Publisher | University of Bradford, Centre for Skin Sciences, Division of Medical Sciences, School of Life Sciences |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Thesis, doctoral, PhD |
| 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>. |
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