An integrative bioinformatics approach for analyses of multi-level transcriptional regulation and three-dimensional organization in the epidermis and skin appendages. Exploring genomic transcriptional profiles of the distinct stages of hair follicle and sweat gland development and analyses of mechanism integrating the transcriptional regulation, linear and high-order genome organization within epidermal differentiation complex in keratinocytes.

Description

The transcription in the eukaryotic cells involves epigenetic regulatory
mechanisms that control local and higher-order chromatin remodelling. In the
skin, keratinocyte-specific genes are organized into distinct loci including
Epidermal Differentiation Complex (EDC) and Keratin type I/II loci. This thesis
introduces bioinformatics approaches to analyze multi-level regulatory
mechanisms that control skin development and keratinocyte-specific
differentiation.
Firstly, integration of gene expression data with analyses of linear genome
organization showed dramatic downregulation of the genes that comprise
large genomic domains in the sweat glands including EDC locus, compared to
ii
hair follicles, suggesting substantial differences in global genome rearrangement
during development of these two distinct skin appendages.
Secondly, comparative analysis of the genetic programmes regulated in
keratinocytes by Lhx2 transcription factor and chromatin remodeler Satb1
revealed that significant number of their target genes is clustered in the
genome. Furthermore, it was shown in this study that Satb1 target genes are
lineage-specific.
Thirdly, analysis of the topological interactomes of Loricrin and Keratin 5 in
hair follicle steam cells revealed presence of the cis- and trans-interactions
and lineage specific genes (Wnt, TGF-beta/activin, Notch, etc.). Expression
levels of the genes that comprise interactomes show correlation with their
histone modification status.
This study demonstrates the crucial role for integration of transcription factormediated
and epigenetic regulatory mechanisms in establishing a proper
balance of gene expression in keratinocytes during development and
differentiation into distinct cell lineages and provides an integrated
bioinformatics platform for further analyses of the changes in global
organization of keratinocyte-specific genomic loci in normal and diseased
skin.

Links & Downloads

1. http://hdl.handle.net/10454/5658

Tags

Bioinformatics

Microarray

ChIP-on-chip

Transcriptional regulation

Three-dimensional genome organization

Hair follicle

Sweat gland

Keratinocytes

Additional Fields

Identifer	oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/5658
Date	January 2013
Creators	Poterlowicz, Krzysztof
Contributors	Botchkarev, Vladimir A., Peng, Yonghong
Publisher	University of Bradford, 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>.