Role of BRD4 in hematopoietic differentiation of embryonic stem cells

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...

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Bibliographic Details
Published in:Epigenetics 2014-04, Vol.9 (4), p.566-578
Main Authors: Rodriguez, Ramon M, Suarez-Alvarez, Beatriz, Salvanés, Ruben, Huidobro, Covadonga, Toraño, Estela G, Garcia-Perez, Jose L, Lopez-Larrea, Carlos, Fernandez, Agustin F, Bueno, Clara, Menendez, Pablo, Fraga, Mario F
Format: Article
Language:English
Subjects:
BRD4
bromodomain
Cell Differentiation
Cell Line
differentiation
DNA Methylation
Embryonic Stem Cells - cytology
Embryonic Stem Cells - metabolism
Epigenesis, Genetic
Fetal Blood - cytology
Hematopoiesis
Hematopoietic Stem Cells - cytology
Hematopoietic Stem Cells - metabolism
Humans
Infant, Newborn
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Proto-Oncogene Proteins c-myc - genetics
Proto-Oncogene Proteins c-myc - metabolism
Research Paper
Signal Transduction
stem cells
Transcription Factors - genetics
Transcription Factors - metabolism
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Summary: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.
ISSN:1559-2294
1559-2308
DOI:10.4161/epi.27711