DOI
https://doi.org/10.25772/MHNX-3E92
Defense Date
2017
Document Type
Thesis
Degree Name
Master of Science
Department
Human Genetics
First Advisor
Joyce A. Lloyd
Abstract
Sickle cell disease and β-thalassemia affect millions of people worldwide. γ-globin is the fetal counterpart to the adult β-globin. Research has shown that affected patients with higher than normal γ-globin show less severe symptoms. Therefore, reversing or preventing the hemoglobin switch from γ- to β- globin is a promising avenue of research for treating these diseases. KLF1 is an erythroid transcription factor involved in hemoglobin switching. Herein, we show that KLF1 directly regulates the γ-globin repressor gene LRF in both the mouse and human systems. KLF1 may also directly activate γ-globin expression by binding the promoter. In human HUDEP-2 cells, an increase in γ-globin expression is seen upon modest knockdown (~50%) of KLF1, whereas normal amounts of KLF1 are observed upon robust knockdown (>75%) of KLF1. The data suggest that KLF1 plays both a positive and negative role in γ-globin expression.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
7-27-2017