TBX3: A novel regulator of AGO2/siRISC-mediated retrotransposon silencing in cell differentiation

Sushmitha Ramakrishna
PhD Student
Department of Biochemistry

Date: February 5, 2024
Time: 1:00 p.m. to 2:00 p.m. 
Room: CSF 1302

Abstract:

Tbx3, a transcriptional factor, plays a crucial role in the self-renewal and pluripotency of mouse embryonic stem cells (mESCs) during early development in animals. Tbx3 binds to genes through its specific motif called Tbx3 binding motif in the gene and regulates their expression. Argonaute 2 (AGO2) is a key component of the siRNA-induced silencing complex (siRISC), responsible for post-transcriptional gene regulation in the cytoplasm. In mouse embryonic stem cells, the activation of retrotransposons such as LINE1 can lead to genome instability, and they also interact with regulatory factors to influence chromatin domain boundaries. AGO2, in conjunction with siRNAs, is essential for suppressing retrotransposons in mouse embryonic stem cells. However, the nuclear functions of AGO2, particularly in post-transcriptional gene silencing, are not fully understood. My research aims to address the gap in understanding the explicit involvement of siRISC in mammalian gene regulation and the molecular events driving stem-like characteristics. Here, we show that Tbx3 interacts with AGO2 and the siRISC in mouse embryonic stem cells with implications in the regulation of target gene expression. Additionally, domain deletion and point mutation analysis of Tbx3 revealed that the DNA-binding and the transcriptional repressor functions are dispensable for Tbx3 interaction with AGO2. These preliminary findings indicate Tbx3 as a novel regulator of siRNA-guided gene silencing in mouse embryonic stem cells. The potential outcome of this research is to provide insights into the mechanisms of Tbx3 in AGO2-mediated retrotransposon repression and the influence of Tbx3 on cell fate decisions dependent on transposable elements.