NC2: Tubby Regulates Estrogen Related Receptor Beta (Esrrβ)

POSTER (Image):


PRESENTER: Adrienne S. Bugayong

AUTHORS: Adrienne S. Bugayong1,3, Peipei Pan1, Lorena P. Samentar1,3, Arnold Salazar1, Durin Uddin1, Josue Portillo1,  Nora B. Caberoy1,2

MENTOR: Dr. Nora B. Caberoy1


A spontaneous mutation in tubby gene causes blindness, hearing loss, and obesity in mice. A combination of these phenotype is seen in rare human syndromes with unknown mechanisms. Thus, the overall goal of this study is to elucidate the role of tubby in the development of these disease phenotypes. Tubby has extra-and intracellular functions, but these do not fully explain how a single mutation in the gene led to three diseases. Thus, this study aims to define the molecular pathways involving tubby by identifying its interacting proteins and the genes that it regulates. Here, we identified Estrogen Related Receptor Beta (Esrrβ) as one of the proteins that interact with tubby in vitro and in vivo. Tubby and Esrrβ both colocalize in the retina. We also demonstrated that Esrrβ is a gene regulated by tubby. Esrrβ expression is decreased in tubby mutant mice in both mRNA and protein levels. Further analysis showed that tubby binds to the promoter of Esrrβ through the estrogen-related receptor response element (ERRE) and activates transcription of Esrrβ. In addition, we also show that tubby translocates into the nucleus and associates with the basal transcription machinery. These findings indicate that tubby is a transcription factor that regulates expression of Esrrβ. Esrrβ is associated with retinal degeneration, hearing loss, and obesity which are similar to tubby mutant phenotypes. Our findings provide a novel mechanistic insight on how tubby maintains healthy vision, and hearing, and proper energy balance through Esrrb induction.

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