Targeting transcription factor binding sites of the interleukin 7 receptor gene using CRISPR/CAS9 genome editing

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Çetin, Ronay (2017) Targeting transcription factor binding sites of the interleukin 7 receptor gene using CRISPR/CAS9 genome editing. [Thesis]

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Abstract

The interleukin 7 cytokine receptor protein (IL-7R) encoded by the il-7r gene is expressed in immune system cells and it allows these cells to be signaled by the IL-7 survival factor. Mutations in the IL-7R pathway are associated with primary immunodeficiency diseases. Polymorphisms in the IL-7R gene are directly linked to T-cell acute lymphoblastic leukemia (T-ALL) and multiple sclerosis (MS). These findings point to the importance of this receptor in health. We have assessed the transcription mechanism of the IL-7R gene in T lymphocytes. We identified the functional significance of transcription factors that bind to IL-7R gene control elements. To this end, we generated mutations in the IL- 7R gene by using CRISPR/Cas9 mediated genome editing. We targeted NF-kB binding site in the enhancer and RORgT and Gfi1 binding sites in intron 2 of the IL-7R gene. We identified the significance of these mutations on IL-7R expression. We performed chromatin immunoprecipitation (ChIP) experiments to reveal the binding abilities of transcription factors to the IL-7R gene targeted with CRISPR/Cas9. In this study, we identified important transcription factors that control the survival of lymphocytes of the immune system.
Item Type: Thesis
Additional Information: Yükseköğretim Kurulu Tez Merkezi Tez No: 478667.
Uncontrolled Keywords: T lymphocyte. -- Interleukin-7 receptor. -- CRISPR/Cas9. -- Genome engineering. -- Regulation of transcription. -- T lenfosit, İnterlökin-7 almacı. -- CRISPR/Cas9. -- Genom mühendisliği. -- Transkripsiyon düzenlenmesi.
Subjects: T Technology > TA Engineering (General). Civil engineering (General) > TA164 Bioengineering
Divisions: Faculty of Engineering and Natural Sciences > Academic programs > Biological Sciences & Bio Eng.
Faculty of Engineering and Natural Sciences
Depositing User: IC-Cataloging
Date Deposited: 07 May 2018 14:27
Last Modified: 26 Apr 2022 10:21
URI: https://research.sabanciuniv.edu/id/eprint/34692

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