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 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.
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.
Ramon M
RM
Rodriguez
Department of Immunology; Hospital Universitario Central de Asturias; Oviedo, Spain.
Beatriz
B
Suarez-Alvarez
Department of Immunology; Hospital Universitario Central de Asturias; Oviedo, Spain.
Ruben
R
Salvanés
Cancer Epigenetics Laboratory; Instituto Universitario de Oncología del Principado de Asturias (IUOPA); HUCA; Universidad de Oviedo; Oviedo, Spain; MRC Human Genetics Unit; Institute of Genetics and Molecular Medicine; University of Edinburgh; Western General Hospital; Edinburgh, UK.
Covadonga
C
Huidobro
Cancer Epigenetics Laboratory; Instituto Universitario de Oncología del Principado de Asturias (IUOPA); HUCA; Universidad de Oviedo; Oviedo, Spain.
Estela G
EG
Toraño
Department of Human DNA Variability; Pfizer-University of Granada and Andalusian Government Center for Genomics and Oncology (GENYO); Granada, Spain.
Jose L
JL
Garcia-Perez
Department of Immunology; Hospital Universitario Central de Asturias; Oviedo, Spain; Fundacion Renal "Íñigo Álvarez de Toledo"; Madrid, Spain.
Carlos
C
Lopez-Larrea
Cancer Epigenetics Laboratory; Instituto Universitario de Oncología del Principado de Asturias (IUOPA); HUCA; Universidad de Oviedo; Oviedo, Spain.
Agustin F
AF
Fernandez
Josep Carreras Leukemia Research Institute; Barcelona, Spain; Centre for Genomics and Oncological Research (GENYO); Pfizer/University of Granada/Andalusian Government; Granada, Spain.
Clara
C
Bueno
Josep Carreras Leukemia Research Institute; Barcelona, Spain; Instituciò Catalana de Reserca i Estudis Avançats (ICREA); Barcelona, Spain.
Pablo
P
Menendez
Cancer Epigenetics Laboratory; Instituto Universitario de Oncología del Principado de Asturias (IUOPA); HUCA; Universidad de Oviedo; Oviedo, Spain; Department of Immunology and Oncology; Centro Nacional de Biotecnología/CNB-CSIC; Cantoblanco; Madrid, Spain.
Mario F
MF
Fraga
D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D002460:Cell Line; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D044127:Epigenesis, Genetic; D005312:Fetal Blood / Q000166:cytology; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000092468:Bromodomain Containing Proteins
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; C441289:BRD4 protein, human; D000092468:Bromodomain Containing Proteins; C489427:MYC protein, human
BRD4; bromodomain; differentiation; hematopoiesis; stem cells