Role of BRD4 in hematopoietic differentiation of embryonic stem cells

BRD4 在胚胎干细胞造血分化中的作用

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作者:Ramon M Rodriguez, Beatriz Suarez-Alvarez, Ruben Salvanés, Covadonga Huidobro, Estela G Toraño, Jose L Garcia-Perez, Carlos Lopez-Larrea, Agustin F Fernandez, Clara Bueno, Pablo Menendez, Mario F Fraga

Abstract

The bromodomain and extra terminal (BET) protein family member BRD4 is a transcriptional regulator, critical for cell cycle progression and cellular viability. Here, we show that BRD4 plays an important role in embryonic stem cell (ESC) regulation. During differentiation of ESCs, BRD4 expression is upregulated and its gene promoter becomes demethylated. Disruption of BRD4 expression in ESCs did not induce spontaneous differentiation but severely diminished hematoendothelial potential. Although BRD4 regulates c-Myc expression, our data show that the role of BRD4 in hematopoietic commitment is not exclusively mediated by c-Myc. Our results indicate that BRD4 is epigenetically regulated during hematopoietic differentiation ESCs in the context of a still unknown signaling pathway.

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