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Identifier |
000426384 |
Title |
Chromatin conformation and chromosomal organization during the activation of T-cells |
Alternative Title |
Μελέτη της χρωματινικής διαμόρφωσης και της χρωμοσωμικής οργάνωσης κατά την ενεργοποίηση Τ-λεμφοκυττάρων |
Author
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Κλωνιζάκης, Αντώνιος Μ.
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Thesis advisor
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Νικολάου, Χριστόφορος
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Reviewer
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Σπηλιανάκης, Χαράλαμπος
Τζαμαρίας, Δημήτριος
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Abstract |
Gene expression and regulation represent crucial processes that control every aspect of eukaryotic life.
3D genome organization has emerged as an additional layer of transcriptional control, through
mechanisms that are not well perceived. In this work, SATB1 was studied in mouse cells. Satb1 is
expressed in specific cells, such as double positive T-cells of the thymus. SATB1 has been shown to
create loops and other three-dimensional structures that ultimately lead to the regulation of gene
expression. Using a conditional knockout mouse line, in which the gene is deleted from double positive
T-cells, we show autoimmunity development. Using next generation sequencing experiments, we
describe in detail the molecular profile of thymocytes that have abolished Satb1. Widespread changes
were observed in the expression levels of genes, accessibility of chromatin, levels of DNA methylation
but also in the three dimensional contacts between multiple genomic loci. We propose a model,
according to which, the loss of Satb1 in thymocytes leads to the developmental arrest of double
positive T-cells and to the degeneration of the thymus due to malfunctioning cell to cell communication
events between T-cells and thymus epithelial cells. The above findings partially explain the
development of autoimmunity following the loss of Satb1 in thymocytes.
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Language |
English |
Subject |
3D genome organization |
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Autoimmunity |
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Gene expression |
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Gene regulation |
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Αυτοανοσία |
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Γονιδιακή έκφραση |
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Γονιδιακή ρύθμιση |
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Τρισδιάστατη οργάνωση γονιδιώματος |
Issue date |
2019-11-29 |
Collection
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School/Department--School of Sciences and Engineering--Department of Biology--Post-graduate theses
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Type of Work--Post-graduate theses
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Permanent Link |
https://elocus.lib.uoc.gr//dlib/b/3/9/metadata-dlib-1575022836-897610-3825.tkl
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Views |
490 |