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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

Autoimmunity

Gene expression

Gene regulation

Αυτοανοσία

Γονιδιακή έκφραση

Γονιδιακή ρύθμιση

Τρισδιάστατη οργάνωση γονιδιώματος

Issue date