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

BMC Biology

Juan José Romero¹  Paula Verneri¹  Marcos Francia¹  María Cecilia De Rossi¹  Camila Oses¹  Camila Vázquez Echegaray¹  Alejandra Guberman²  Valeria Levi³ 

[1] Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET-Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, C1428EGA, Buenos Aires, Argentina;Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET-Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, C1428EGA, Buenos Aires, Argentina;Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, C1428EGA, Buenos Aires, Argentina;Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET-Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, C1428EGA, Buenos Aires, Argentina;Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, C1428EGA, Buenos Aires, Argentina;

关键词: Embryonic stem cells;    Cytoskeleton;    Nuclear morphology;    OCT4;    Transcription factors dynamics;    Fluorescence correlation spectroscopy;   

DOI  :  10.1186/s12915-021-01207-w

来源: Springer

【 摘 要 】

BackgroundThe cytoskeleton is a key component of the system responsible for transmitting mechanical cues from the cellular environment to the nucleus, where they trigger downstream responses. This communication is particularly relevant in embryonic stem (ES) cells since forces can regulate cell fate and guide developmental processes. However, little is known regarding cytoskeleton organization in ES cells, and thus, relevant aspects of nuclear-cytoskeletal interactions remain elusive.ResultsWe explored the three-dimensional distribution of the cytoskeleton in live ES cells and show that these filaments affect the shape of the nucleus. Next, we evaluated if cytoskeletal components indirectly modulate the binding of the pluripotency transcription factor OCT4 to chromatin targets. We show that actin depolymerization triggers OCT4 binding to chromatin sites whereas vimentin disruption produces the opposite effect. In contrast to actin, vimentin contributes to the preservation of OCT4-chromatin interactions and, consequently, may have a pro-stemness role.ConclusionsOur 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 affecting pluripotency and cell fate.

【 授权许可】

CC BY