Transcriptional regulation of IL-7R alpha gene in T lymphocytes
Akçay, İzzet Mehmet (2010) Transcriptional regulation of IL-7R alpha gene in T lymphocytes. [Thesis]
Official URL: http://192.168.1.20/record=b1304380 (Table of Contents)
Interleukin-7 signaling is vital for the proper functioning of the immune system. It is required for the development and homeostasis of lymphocytes. This signaling is greatly controlled by the regulation of IL-7 Receptor alpha expression, whereas IL-7 production is thought to be constant. As the dramatic changes during the development of T lymphocytes illustrate, IL-7R alpha expression is strictly regulated. IL-7R alpha expression also varies with the activation stage of mature T cells. Therefore, the molecular events underlying the regulation of IL-7R alpha in T lymphocytes has been an intensive research area since its discovery. The glucocorticoid receptor has been known to induce transcription of IL-7R alpha, whereas Gfi1 transcription factor represses its expression. Here, we investigated if glucocorticoid stimulation induced IL-7R alpha in T cells due to the posttranscriptional silencing of Gfi1. We performed real time reverse transcriptase polymerase chain reaction (RT-PCR) analyses of several miRNAs predicted to target Gfi1 mRNA upon dexamethasone (a glucocorticoid) stimulation. Our data suggested that Gfi1 was not silenced by RNA interference. We also investigated the roles of different Gfi1 domains in the repression of IL- 7R alpha expression. By retroviral overexpression studies in T lymphocytes, we demonstrated that none of this transcription factor's domains was capable of exerting the function of Gfi1 on the IL-7R alpha gene by itself. Moreover, the SNAG domain and the Zinc Fingers were specifically required for this function. Finally, we showed that overexpression of the transcription factors Gfi1b and Foxp3 also repressed dexamethasone-induced IL-7R alpha gene in T cells.
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