Date of Award

8-1-2013

Degree Name

Master of Science

Department

Molecular Cellular and Systemic Physiology

First Advisor

Collard, Michael

Abstract

Deformed epidermal autoregulatory factor-1 (DEAF1) is a transcription factor that has been shown to be essential in development and immunity in Drosophila (Veraksa et al. 2002; Reed et al. 2008) and a contributor to neural tube defects, cancer, and depression in mammals (Hahm et al. 2004; Cubeddu et al. 2006; Iyo et al. 2009). Recently, it has been determined that DEAF1 plays a role in development of peripheral immune tolerance in the lymph nodes, and that variant isoforms and deficiencies of DEAF1 may contribute to development of type I diabetes (Yip et al. 2009). Eukaryotic initiation factor 4 gamma 3 (Eif4g3) has reduced expression in type I diabetics and in Deaf1 deficient mice (Yip et al. 2013). Mouse embryo fibroblasts (MEF) lacking Deaf1 were used as a model system to examine the role of Deaf1 in target gene transcription. Loss of Deaf1 reduced Eif4g3 mRNA levels. DEAF1 was shown to be physically associated with the Deaf1 and Eif4g3 transcriptional promoters. Repressive histone modifications and DNA methylation were absent in Eif4g3 promoter region. These studies indicate that DEAF1 expression positively influences Deaf1 and Eif4g3 transcription by association with the promoters through direct DNA binding and not through changes in DNA or histone modification.

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