UNDERSTANDING HEPATIC REV-ERBa INTERACTING PARTNERS AS IT PEAKS AND TROUGHS THROUGH THE CIRCADIAN DAY

In this thesis the reader will find a body of work that describes new and exciting data about the nuclear receptors REV-ERBa and REV-ERBREV-ERBs are interesting proteins to understand because they play important roles in the circadian clock and in the regulation of metabolism on a variety of tissues. Understanding how a factor can link both the clock and metabolism could be the key to understanding the negative effects that circadian misalginment has on metabolic and overall health. In chapter 1 we describe the current knowledge of REV-ERBs and their known roles in the circadian clock and metabolism. We also point out the main aims of this project in understanding what proteins and protein complexes does REV-ERB interact with in order to regulate metabolic and clock genes in a tissue specific manner. In chapter 2 we describe our methodology and the preliminary findings of our proteomics data. In chapter 3 we dive into our first target for follow up the discovery that the HDAC1/SIN3a complex interacts with REV-ERB. In chapter 4 we delve into the second novel finding that REV-ERB gets SUMOylated in a rhythmic manner. Finally we discovered that REV-ERBs play an important role in the regulation of SUMO3 expression in the liver.