Cancer Epigenetics Laboratory; Instituto Universitario de Oncología del Principado de Asturias (IUOPA); HUCA; Universidad de Oviedo; Oviedo, Spain; Department of Immunology; Hospital Universitario Central de Asturias; Oviedo, Spain.
Department of Immunology; Hospital Universitario Central de Asturias; Oviedo, Spain.
Epigenetics. 2014 Apr;9(4):566-78. doi: 10.4161/epi.27711. Epub 2014 Jan 20.
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.
溴结构域和末端结构域（BET）蛋白家族成员 BRD4 是一种转录调节剂，对于细胞周期进程和细胞活力至关重要。在这里，我们表明 BRD4 在胚胎干细胞（ESC）调节中发挥重要作用。在 ESC 的分化过程中，BRD4 的表达上调，其基因启动子去甲基化。在 ESC 中破坏 BRD4 的表达不会诱导自发分化，但严重降低了造血内皮潜能。尽管 BRD4 调节 c-Myc 的表达，但我们的数据表明 BRD4 在造血分化中的作用并非完全由 c-Myc 介导。我们的结果表明，BRD4 在造血分化过程中在一个尚不清楚的信号通路的背景下受到表观遗传调控。
