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Identifier

000355261

Title

Μεταγραφική ρύθμιση του γενετικού τόπου μίας κυτοκίνης και του υποδοχέα της μέσω χρωμοσωμικών αλληλεπιδράσεων

Author

Δεληγιάννη, Χρυσούλα

Thesis advisor

Σπηλιανάκης, Χαράλαμπος

Reviewer

Παπαματθαιάκης, Ιωσήφ

Abstract

The development of the immune system and the host response to microbial infections rely on the activation and silencing of numerous, differentially expressed genes. Utilizing an in vivo immunological system, namely the differentiation of the naïve CD4+ helper T cells in T(helper)H1 and TH2 cells, we focused on the transcriptional regulation of interferon gamma (IFNγ, m.chr. 10), interferon gamma receptor 1 (IFNγR1, m. chr.10) and interferon gamma receptor 2 (IFNγR2, m. chr.16) genomic loci. Our goal was to investigate the hypothesis that a cytokine or a ligand and its receptors are co-regulated in the genomic level. DNA-FISH experiments revealed that the IFNγ and IFNγR1 loci are in close proximity in cell types that they are expressed such as Naïve and TH1 CD4+ cells, in a monoallelic manner, but they are apart in TH2 cells, where they are not expressed. Additionally, IFNγ and IFNγR2 loci colocalize in Th2 cells. The expression profile of IFNγ and IFNγR1 genes in the single cell level, performing RNA FISH experiments, demonstrated that IFNγ is expressed biallelically, in TH1 restimulated cells, whereas IFNγR1 is expressed in Naïve and TH1 cells, solely from the allele that colocalizes with the IFNγ locus. Therefore, we showed that the physical approach of the two loci has a functional significance, in cell types which are developmentally predisposed or determined to express these genes. Moreover, ACT (Associated Chromosome Trap) experiments using the promoter region of IFNγR1 showed a different pattern of interacting fragments between Naïve, TH1 and TH2 cells. Finally, it was hypothesized that the subnuclear compartment that IFNγ-IFNγR1 interaction takes place is an RΝΑ PollI factory, suggesting a role for this subnuclear compartment in the transcriptional regulation of these genetic loci. Further investigation utilizing biochemical approaches will help us identify the protein complexes that mediate this type of intra- and inter-chromosomal interactions.

Physical description

45 σ. : πιν. ; 30 εκ.

Language

Greek

Subject

Cytokines immunology

Issue date

2008-12-15

Collection

School/Department--School of Medicine--Department of Medicine--Post-graduate theses

Type of Work--Post-graduate theses

Notes