GATA-1 REPROGRAMS AVIAN MYELOMONOCYTIC CELL-LINES INTO EOSINOPHILS, THROMBOBLASTS, AND ERYTHROBLASTS

被引:353
作者
KULESSA, H
FRAMPTON, J
GRAF, T
机构
[1] Differentiation Programme, European Molecular Biology Lab.
关键词
HEMATOPOIETIC CELL DIFFERENTIATION; LINEAGE COMMITMENT; GATA-1; VIRAL ONCOGENES; TRANSCRIPTION FACTORS;
D O I
10.1101/gad.9.10.1250
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The transcription factor GATA-1 is expressed in early hematopoietic progenitors and specifically down-regulated in myelomonocytic cells during lineage determination. Our earlier observation that the differentiation of Myb-Ets-transformed chicken hematopoietic progenitors into myeloblasts likewise involves a GATA-1 down-regulation, whereas expression is maintained in erythroid, thrombocytic, and eosinophilic derivatives, prompted us to study the effect of forced GATA-1 expression in Myb-Ets-transformed myeloblasts. We found that the factor rapidly suppresses myelomonocytic markers and induces a reprogramming of myeloblasts into cells resembling either transformed eosinophils or thromboblasts. In addition, we observed a correlation between the level of GATA-1 expression and the phenotype of the cell, intermediate levels of the factor being expressed by eosinophils and high levels by thromboblasts, suggesting a dosage effect of the factor. GATA-1 can also induce the formation of erythroblasts when expressed in a myelomonocytic cell line transformed with a Myb-Ets mutant containing a lesion in Ets. These cells mature into erythrocytes following temperature-inactivation of the Ets protein. finally, the factor can reprogram a v-Myc-transformed macrophage cell line into myeloblasts, eosinophils, and erythroblasts, showing that the effects of GATA-1 are not limited to Myb-Ets-transformed myeloblasts. Our results suggest that GATA-1 is a lineage-determining transcription factor in transformed hematopoietic cells, which not only activates lineage-specific genetic programs but also suppresses myelomonocytic differentiation. They also point to a high degree of plasticity of transformed hematopoietic cells.
引用
收藏
页码:1250 / 1262
页数:13
相关论文
共 66 条
[1]   THE SCL GENE-PRODUCT - A POSITIVE REGULATOR OF ERYTHROID-DIFFERENTIATION [J].
APLAN, PD ;
NAKAHARA, K ;
ORKIN, SH ;
KIRSCH, IR .
EMBO JOURNAL, 1992, 11 (11) :4073-4081
[2]   Reversibility of the differentiated state in somatic cells [J].
Baron, Margaret H. .
CURRENT OPINION IN CELL BIOLOGY, 1993, 5 (06) :1050-1056
[3]   FUNCTIONAL ANTAGONISM BETWEEN C-JUN AND MYOD PROTEINS - A DIRECT PHYSICAL ASSOCIATION [J].
BENGAL, E ;
RANSONE, L ;
SCHARFMANN, R ;
DWARKI, VJ ;
TAPSCOTT, SJ ;
WEINTRAUB, H ;
VERMA, IM .
CELL, 1992, 68 (03) :507-519
[4]   CHICKEN HEMATOPOIETIC-CELLS TRANSFORMED BY 7 STRAINS OF DEFECTIVE AVIAN LEUKEMIA VIRUSES DISPLAY 3 DISTINCT PHENOTYPES OF DIFFERENTIATION [J].
BEUG, H ;
VONKIRCHBACH, A ;
DODERLEIN, G ;
CONSCIENCE, JF ;
GRAF, T .
CELL, 1979, 18 (02) :375-390
[5]   REVERSIBILITY OF DIFFERENTIATION AND PROLIFERATIVE CAPACITY IN AVIAN MYELOMONOCYTIC CELLS TRANSFORMED BY TSE26 LEUKEMIA-VIRUS [J].
BEUG, H ;
BLUNDELL, PA ;
GRAF, T .
GENES & DEVELOPMENT, 1987, 1 (03) :277-286
[6]   DIFFERENTIATION REQUIRES CONTINUOUS ACTIVE CONTROL [J].
BLAU, HM .
ANNUAL REVIEW OF BIOCHEMISTRY, 1992, 61 :1213-1230
[7]   PLASTICITY OF THE DIFFERENTIATED STATE [J].
BLAU, HM ;
PAVLATH, GK ;
HARDEMAN, EC ;
CHIU, CP ;
SILBERSTEIN, L ;
WEBSTER, SG ;
MILLER, SC ;
WEBSTER, C .
SCIENCE, 1985, 230 (4727) :758-766
[8]   ECTOPIC EXPRESSION OF A CONDITIONAL GATA-2 ESTROGEN-RECEPTOR CHIMERA ARRESTS ERYTHROID-DIFFERENTIATION IN A HORMONE-DEPENDENT MANNER [J].
BRIEGEL, K ;
LIM, KC ;
PLANK, C ;
BEUG, H ;
ENGEL, JD ;
ZENKE, M .
GENES & DEVELOPMENT, 1993, 7 (06) :1097-1109
[9]   DIFFERENTIATION AND GENE-REGULATION - EDITORIAL OVERVIEW [J].
BROWN, DD ;
DAWID, IB .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 1994, 4 (05) :627-629
[10]   SYNERGISTIC ACTIVATION OF THE CHICKEN MIM-1 GENE BY V-MYB AND C/EBP TRANSCRIPTION FACTORS [J].
BURK, O ;
MINK, S ;
RINGWALD, M ;
KLEMPNAUER, KH .
EMBO JOURNAL, 1993, 12 (05) :2027-2038