DIFFERENT DYNAMICAL ORGANIZATION OF OCT4 IN PLURIPOTENT AND TERMINALLY DIFFERENTIATED CELLS.

VAZQUEZ ECHEGARAY, CAMILA; FRANCIA, MARCOS; LEVI, VALERIA; PAULA VERNERI; MARIA VICTORIA PETRONE; ALEJANDRA GUBERMAN; CAMILA OSES; AYELEN TORO

buenos aires

Congreso; Xth Meeting of the Latin American Society for Developmental Biology; 2019

Latin American Society for Developmental Biology

The achievement and maintenance of pluripotency requires specific transcription factors (TFs) such as Oct4, Sox2 and Nanog, that induce genes required for pluripotency and repress others involved in differentiation in pluripotent stem cells (PSC). Besides their levels, the distribution and interactions of these TFs with chromatin and their subnuclear localization impact on gene expression. Therefore, it is essential to explore the dynamical organization of TFs to fully understand their role on transcription regulation. Here, we examine how Oct4 distributes in the nucleus of PSC and terminally differentiated cells and analyzed changes in its dynamical organization. For this aim, we constructed stable cell lines expressing Oct4 fused to the fluorescent protein YPet. We found that, in undifferentiated cells, Oct4 partitioned between the nucleoplasm and a few chromatin-dense foci, whereas the number of foci increased in differentiated cells. These foci colocalized with regions of condensed chromatin, and their formation does not involve liquid phase condensation. When comparing the dynamics of the interaction of Oct4 and its chromatin targets, we found differences in residence times and bound fractions between the different cell lines. In conclusion, the dynamical reorganization of Oct4 may contribute to modulate its role at differentiation or during reprogramming. Overall, these evidences contribute to the understanding of the molecular mechanisms involved in cell fate decisions.