Understanding the Structure and Function of the N-terminal Domain of the Thyroid Receptor

Gene transcription relies on transcription factors that interact with DNA to control the rate of transcription. This thesis describes one such transcription factor, the thyroid hormone receptor, which is a nuclear receptor that binds to specific DNA sequences that is activated by the thyroid hormone. The research is this thesis is split up into two distinct areas: understanding the N-terminal domain of the thyroid receptor protein and understanding the interaction of the N-terminal domain of the thyroid receptor to DNA. Complete understanding of the N-terminal domain remains elusive as structural information such as 3D structures remain unavailable in part because today’s structural studies are unable to obtain high resolution images of flexible and intrinsically disordered properties as is this case with the N-terminal domain. The specificity of the interaction between the N-terminal domain and DNA is unknown as well. Overall, this study reveals that there are specific interactions between the N-terminal domain and DNA that affect both structure and function of the thyroid receptor. Some of these sequences involved in these interactions appear to be conserved across a wide range of nuclear receptors and genomic DNA. The impact of these studies could greatly improve our understanding of both the thyroid receptor and nuclear receptors that might lead to improved understanding of the physiological processes in the human body and treatment of disease.