Nucleus-cytoskeleton communication impacts on OCT4-chromatin interactions in embryonic stem cells

ROMERO, JUAN JOSÉ; DE ROSSI, MARÍA CECILIA; OSES, CAMILA; ECHEGARAY, CAMILA VÁZQUEZ; VERNERI, PAULA; FRANCIA, MARCOS; GUBERMAN, ALEJANDRA; LEVI, VALERIA

BMC BIOLOGY

BIOMED CENTRAL LTD

Año: 2022 vol. 20

1741-7007

Background: The cytoskeleton is a key component of the system responsible for transmitting mechanical cuesfrom the cellular environment to the nucleus, where they trigger downstream responses. This communication isparticularly relevant in embryonic stem (ES) cells since forces can regulate cell fate and guide developmentalprocesses. However, little is known regarding cytoskeleton organization in ES cells, and thus, relevant aspects ofnuclear-cytoskeletal interactions remain elusive.Results: We explored the three-dimensional distribution of the cytoskeleton in live ES cells and show that thesefilaments affect the shape of the nucleus. Next, we evaluated if cytoskeletal components indirectly modulate thebinding of the pluripotency transcription factor OCT4 to chromatin targets. We show that actin depolymerizationtriggers OCT4 binding to chromatin sites whereas vimentin disruption produces the opposite effect. In contrast toactin, vimentin contributes to the preservation of OCT4-chromatin interactions and, consequently, may have a prostemnessrole.Conclusions: Our results suggest roles of components of the cytoskeleton in shaping the nucleus of ES cells,influencing the interactions of the transcription factor OCT4 with the chromatin and potentially affectingpluripotency and cell fate.