Date of Award

Spring 5-2021

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biological Sciences

First Advisor

Jamie Newman

Abstract

In order for any function to occur within a cell, transcription factors must be able to interact with genes. When this occurs, genes are expressed, and ultimately, proteins are translated and perform the specific function that needs to be done within the cell. In order for this to occur, genes must interact with transcription machinery. The Mediator complex recruits transcription factors to genes in order to promote cell-type specific gene expression. The Mediator complex is a multi-protein complex consisting of four modules: head, middle, tail, and kinase. The kinase module is known to dissociate from the rest of the complex in order to phosphorylate other proteins for the purposes of propagating signals. MED12 of the kinase module has been shown to mediate CDK8 function by binding to Cyclin C, allowing for phosphorylation and propagation of signals. Throughout this thesis, I demonstrate MED12’s role in allowing CDK8 function in promoting cell-type specific gene expression. Through the use of siRNA-mediated knockdowns of MED12, it is evident that MED12 plays a role in the initiation of adipogenesis. qRT-PCR and staining confirm this assumption, as there is significantly less adipogenesis occurring in hASCs when MED12 is knocked down. This is further evidenced by reduced expression of early adipogenic markers, most notably, PPAR-γ. If MED12 initiates cell type-specific gene expression of differentiating adipocytes, then it may be used as a target to direct fat formation to reduce the effects of obesity.

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