Relevance of the nucleus-cytoskeleton communication on the dynamics and distribution of the pluripotency transcription factor OCT4 in embryonic stem cells

VERNERI P; ROMERO JJ; DE ROSSI MC; OSES C; VÁZQUEZ ECHEGARAY C; FRANCIA M; LESCURAS AGUILAR JM; GUBERMAN A; LEVI V

Congreso; L Reunión Anual de la Sociedad Argentina de Biofísica; 2022

Cells are constantly exposed to forces that are directly transmitted to the nucleus through the cytoskeleton (CSK). In embryonic stem cells (ESC), mechanical stimuli coming from the extracellular environment are sufficient to trigger the differentiation process and contribute to cell fate decisions. Pluripotency of ESCs depends on certain transcription factors (TFs) - OCT4, SOX2 and NANOG- which induce genes necessary to preserve pluripotency and repress others involved in differentiation. Their nuclear distribution and dynamical interactions with DNA targets play a fundamental role in gene modulation that may impact on cell fate. Relevantly, mechanical forces also affect the nuclear translocation of TFs associated with pluripotency and differentiation. Here, we analyzed if certain cytoskeletal components, which are responsible for the transmission of mechanical stimuli, modulate the dynamical organization and distribution of the pluripotency TF OCT4 in mouse ESCs. We observed that actin depolymerization triggered OCT4 binding to chromatin sites whereas vimentin disruption produced the opposite effect. Furthermore, actin depolymerization promotes a nuclear redistribution of the TFs, triggering its recruitment to nuclear foci formation. Additionally, interfering microtubules polymerization modified the relative concentration of OCT4 in the nucleus with respect to the cytoplasm suggesting an impairment in the shuttling between these compartments. Taken together, our results reveal that cytoskeletal components modulate OCT4 nuclear organization that also includes modifications in TF-chromatin interactions. This dynamical reorganization may ultimately contribute to modulate OCT4 affecting cell fate.