Identifying Regions of The CXCR3 Promotor Required for Activation by FLI1 In Stimulated T-Cells

School Name

Governor's School for Science & Mathematics

Grade Level

12th Grade

Presentation Topic

Cell and Molecular Biology

Presentation Type

Mentored

Mentor

Mentor: Tamara Nowling, Medical University of South Carolina

Oral Presentation Award

1st Place

Abstract

Lupus is an autoimmune disease that causes inflammation of tissues in several important body systems, including the kidney. FLI1 is a transcription factor that regulates hematopoiesis, hemostasis, cell death, and cell cycle. FLI1 regulates CXCR3 expression. CXCR3 is a receptor in the kidney that is key to T-Cell migration to the kidney, and is upregulated by FLI1. It was found previously that reducing levels of FLI1 decreases T-Cell CXCR3 expression in lupus mice. In our lab we focused on lupus nephritis (kidney inflammation) and how we could lessen the upregulation of hCXCR3 to possibly lessen the effects of lupus in the future. In our study we sought to identify the region of the hCXCR3 promoter that is required for activation by FLI1 in stimulated T-cells. We transfected deletion sequences of hCXCR3 and FLI1 into jurkat T-cells. Then we performed a luciferase assay on the transfection to measure the luminescence expression of hCXCR3. We found that the nucleotides between -89 and +200 are important for the upregulation of hCXCR3. Then we tested FLI1 mutants to see how they affected the expression of hCXCR3. The FLI1 DNA binding mutant caused a decrease in expression, and the acetylation and phosphorylation mutant caused an increase in the hCXCR3 expression. From this we can conclude that the region between -89 and +200 includes a key binding site for FLI1 to bind to hCXCR3.

Location

Wall 209

Start Date

3-25-2017 12:15 PM

Presentation Format

Oral and Written

Group Project

No

COinS
 
Mar 25th, 12:15 PM

Identifying Regions of The CXCR3 Promotor Required for Activation by FLI1 In Stimulated T-Cells

Wall 209

Lupus is an autoimmune disease that causes inflammation of tissues in several important body systems, including the kidney. FLI1 is a transcription factor that regulates hematopoiesis, hemostasis, cell death, and cell cycle. FLI1 regulates CXCR3 expression. CXCR3 is a receptor in the kidney that is key to T-Cell migration to the kidney, and is upregulated by FLI1. It was found previously that reducing levels of FLI1 decreases T-Cell CXCR3 expression in lupus mice. In our lab we focused on lupus nephritis (kidney inflammation) and how we could lessen the upregulation of hCXCR3 to possibly lessen the effects of lupus in the future. In our study we sought to identify the region of the hCXCR3 promoter that is required for activation by FLI1 in stimulated T-cells. We transfected deletion sequences of hCXCR3 and FLI1 into jurkat T-cells. Then we performed a luciferase assay on the transfection to measure the luminescence expression of hCXCR3. We found that the nucleotides between -89 and +200 are important for the upregulation of hCXCR3. Then we tested FLI1 mutants to see how they affected the expression of hCXCR3. The FLI1 DNA binding mutant caused a decrease in expression, and the acetylation and phosphorylation mutant caused an increase in the hCXCR3 expression. From this we can conclude that the region between -89 and +200 includes a key binding site for FLI1 to bind to hCXCR3.