An Esrrb and nanog cell fate regulatory module controlled by feed forward loop interactions

Cell fate decisions during development are governed by multi-factorial regulatory mechanisms including chromatin remodeling, DNA methylation, binding of transcription factors to specific loci, RNA transcription and protein synthesis. However, the mechanisms by which such regulatory 'dimensions&...

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Detalles Bibliográficos
Autores: Sevilla, Ana, Papatsenko, Dimitri, Mazloom, Amin R., Xu, Huilei, Vasileva, Ana, Unwin, Richard D., LeRoy, Gary, Chen, Edward Y., Garrett-Bakelman, Francine E., Lee, Dung-Fang, Trinite, Benjamin, Webb, Ryan L., Wang, Zichen, Su, Jie, Gingold, Julian, Melnick, Ari, Garcia, Benjamin A., Whetton, Anthony D., MacArthur, Ben D., Ma'ayan, Avi, Lemischka, Ihor R.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/176522
Acceso en línea:https://hdl.handle.net/2445/176522
Access Level:acceso abierto
Palabra clave:Cèl·lules mare embrionàries
Receptors nuclears (Bioquímica)
Embryonic stem cells
Nuclear receptors (Biochemistry)
Descripción
Sumario:Cell fate decisions during development are governed by multi-factorial regulatory mechanisms including chromatin remodeling, DNA methylation, binding of transcription factors to specific loci, RNA transcription and protein synthesis. However, the mechanisms by which such regulatory 'dimensions' coordinate cell fate decisions are currently poorly understood. Here we quantified the multi-dimensional molecular changes that occur in mouse embryonic stem cells (mESCs) upon depletion of Estrogen related receptor beta (Esrrb), a key pluripotency regulator. Comparative analyses of expression changes subsequent to depletion of Esrrb or Nanog, indicated that a system of interlocked feed-forward loops involving both factors, plays a central part in regulating the timing of mESC fate decisions. Taken together, our meta-analyses support a hierarchical model in which pluripotency is maintained by an Oct4-Sox2 regulatory module, while the timing of differentiation is regulated by a Nanog-Esrrb module.