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Identifier 000382143
Title Συν-ρύθμιση των IFNG και IFNGR1 στο γενωμικό επίπεδο
Alternative Title Co-regulation of IFNG and IFNGR1 at the genomic level
Author Δεληγιάννη, Χρυσούλα.
Thesis advisor Σπηλιανάκης, Χαράλαμπος
Τσατσάνης, Χρήστος
Abstract The development of the immune system and the host immune response to microbial infections rely on the transcriptional activation and silencing of multiple gene loci. By utilizing the differentiation system of naive CD4+, TH1 and TH2 lymphocytes, we focused on the transcriptional regulation of the interferon-γ (Ifnγ, mouse choromosome 10) and interferon-γ receptor 1 (IfnγR1, mouse chromosome 10) genes. So, in the present doctoral thesis we present a model whereby there are long range monoallelic intra-chromosomal associations between the IfnγR1 and Ifnγ loci, in cell types that express the receptor. Expression profile analysis revealed the functional significance of the co-localization, since IfnγR1 is expressed in naive CD4+ and TH1 cells from the allele that is in close physical proximity with the Ifnγ locus. Moreover, the interactions take place in transcription factories, but they are independent of transcription. Importantly, CTCF, a general transcription factor, seems to play a critical role to the aforementioned phenomena. Regarding the functional characterization of the underlying mechanism, here we provide evidence to support the hypothesis that CTCF is recruited to the non-methylated promoter region of IfnγR1 allele, possibly with the help of Τ-bet and sets a pattern of monoallelic co-localization and positive transcriptional regulation of the receptor gene locus.
Language Greek
Issue date 2013-07-16
Collection   School/Department--School of Medicine--Department of Medicine--Doctoral theses
  Type of Work--Doctoral theses
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