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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 Κλωνιζάκης, Αντώνιος Μ.
Thesis advisor Νικολάου, Χριστόφορος
Reviewer Σπηλιανάκης, Χαράλαμπος
Τζαμαρίας, Δημήτριος
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.
Language English
Subject 3D genome organization
Gene expression
Gene regulation
Γονιδιακή έκφραση
Γονιδιακή ρύθμιση
Τρισδιάστατη οργάνωση γονιδιώματος
Issue date 2019-11-29
Collection   Faculty/Department--Faculty of Sciences and Engineering--Department of Biology--Post-graduate theses
  Type of Work--Post-graduate theses
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