Role of BRD4 in hematopoietic differentiation of embryonic stem cells

被引：13
|
作者：
Rodriguez, Ramon M. [1 ,2 ]
Suarez-Alvarez, Beatriz [2 ]
Salvanes, Ruben [2 ]
Huidobro, Covadonga [1 ,3 ]
Torano, Estela G. [1 ]
Garcia-Perez, Jose L. [4 ,5 ]
Lopez-Larrea, Carlos [2 ,6 ]
Fernandez, Agustin F. [1 ]
Bueno, Clara [7 ,8 ]
Menendez, Pablo [7 ,9 ]
Fraga, Mario F. [1 ,10 ]
机构：
[1] Univ Oviedo, Canc Epigenet Lab, IUOPA, HUCA, Oviedo, Spain
[2] Hosp Univ Cent Asturias, Dept Immunol, Oviedo, Spain
[3] Univ Edinburgh, Western Gen Hosp, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland
[4] Univ Granada, Dept Human DNA Variabil, Pfizer, Granada, Spain
[5] Andalusian Govt Ctr Genom & Oncol GENYO, Granada, Spain
[6] Fdn Renal Inigo Alvarez de Toledo, Madrid, Spain
[7] Josep Carreras Leukemia Res Inst, Barcelona, Spain
[8] Univ Granada, Ctr Genom & Oncol Res GENYO, Pfizer, Andalusian Govt, Granada, Spain
[9] ICREA, Barcelona, Spain
[10] CSIC, CNB, Dept Immunol & Oncol, Madrid, Spain
来源：
EPIGENETICS | 2014年 / 9卷 / 04期
关键词：
differentiation; stem cells; BRD4; hematopoiesis; bromodomain; BROMODOMAIN PROTEIN BRD4; PROMOTER DNA METHYLATION; C-MYC; MIDLINE CARCINOMA; GENE-EXPRESSION; S-PHASE; SPECIFICATION; SURVIVAL; LINEAGE; TARGET;
D O I：
10.4161/epi.27711
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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.
引用
收藏
页码：566 / 578
页数：13
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