Regulation of gene transcription during the differentiation of megakaryocytes.
Glycoprotein IIb (GPIIb) is an early and specific marker of the megakaryocytic lineage. Thus studies on the transcriptional regulation of this gene may provide helpful information on the mechanisms controlling cell specificity and differentiation of this lineage. In previous experiments, the promoter of GPIIb gene was isolated and we have shown that a fragment extending 643 bp upstream the transcription start site was able to control the cell specificity of a reporter gene in transfection experiments of different permanent cell lines. Most of the transcriptional activity is contained in an enhancer containing binding sites for members of the GATA and ets transcription factors families. The transcription factor GATA1 is not only a major regulator of the transcription of erythroid genes, but it also regulates the expression of GPIIb and other megakaryocytic genes. We suggest that the lineage specificity and the temporal activation of GPIIb gene during hematopoiesis rely on the activity of a repressor that has been identified on the promoter. To test this hypothesis, we have developed a cell model allowing the study of the megakaryocytes differentiation from very immature progenitors to fully differentiated cells. This model is based on the differentiation of mouse embryonic stem cells. We have obtained megakaryocytes together with erythrocytic and granulo-macrophagic cells. The transfection in these ES cells of GPIIb promoter constructs mutated or not on different regions, including the repressor element will provide important information on the mechanisms controlling gene activation or repression during megakaryocyte differentiation.
Uzan
G
G
CEA, Laboratoire d'Hématologie, INSERM U217, Département de Biologie Moléculaire et Structurale, CEN Grenoble, France.
Prandini
M H
MH
Berthier
R
R
D000818:Animals; D015415:Biomarkers; D001792:Blood Platelets / Q000166:cytology; D002454:Cell Differentiation; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000502:physiology; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; D005786:Gene Expression Regulation; D006410:Hematopoiesis / Q000502:physiology*; D008533:Megakaryocytes / Q000166:cytology*; D051379:Mice; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000096:biosynthesis / Q000235:genetics; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D013234:Stem Cells / Q000166:cytology; D014157:Transcription Factors / Q000502:physiology; D015533:Transcriptional Activation
D015415:Biomarkers; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014157:Transcription Factors