Date of Award

2021

Document Type

Undergraduate Thesis

Degree Name

BS

Department

Biomedical Sciences

Faculty Mentor

Gabriela Gorelik

Abstract

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that primarily affects women. The etiology is not known yet, but genetics and environmental factors trigger the disease. These epigenetic changes modify gene expression and contribute to the development of the disease. It is known that T cells from patients with lupus overexpress genes that may contribute to the onset and progression of the disease. Dr. Gorelik has shown that OGT (O-linked N-acetyl-Glucosamine Transferase), which is an X-linked gene, is overexpressed in women with SLE. OGT adds b-N-acetylglucosamine (O-GlcNAc) to serine and threonine residues of proteins. OGT may play a critical role in chromatin structure by O-GlcNAcylation of histones. Furthermore, O-GlcNAc is considered part of the histone code. The effect of OGT in T cells is unknown, but its overexpression may play a role in T cell dysfunction in lupus. This evidence led us to investigate molecular targets of OGT in T cells, particularly its role in the post-translational modification of histones. This work was done with primary T cells isolated form the peripheral blood of healthy female donors. The cells underwent various treatment and protein expression was analyzed via SDS-PAGE electrophoresis. Our results strongly suggest that H2B is a molecular target of OGT in healthy T cells, and the overexpression of OGT in lupus T cells may increase H2B glycosylation. In consequence, it may also modify chromatin structure, causing changes in gene expression, and may be an epigenetic modulator in lupus, explaining the female preponderance to develop SLE.

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