MYB AND NF-M - COMBINATORIAL ACTIVATORS OF MYELOID GENES IN HETEROLOGOUS CELL-TYPES

被引:253
作者
NESS, SA
KOWENZLEUTZ, E
CASINI, T
GRAF, T
LEUTZ, A
机构
[1] NORTHWESTERN UNIV,DEPT BIOCHEM MOLEC BIOL & CELL BIOL,EVANSTON,IL 60208
[2] EUROPEAN MOLEC BIOL LAB,DIFFERENTIAT PROGRAMME,W-6900 HEIDELBERG,GERMANY
关键词
MYB ONCOGENE; C/EBP-LIKE FACTORS; HEMATOPOIESIS; TRANSCRIPTION FACTORS; GENE EXPRESSION;
D O I
10.1101/gad.7.5.749
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The c-Myb transcription factor regulates the differentiation of immature erythroid, lymphoid, and myeloid cells, although only the latter cells become transformed by the v-myb oncogene. These are also the only cells that express the Myb-regulated gene mim-1, suggesting that Myb requires tissue-specific, cooperating factors to activate such genes. Here, we investigated the tissue-specific regulation of the mim-1 promoter and found that it not only contains binding sites for Myb but also for NF-M, a myeloid-specific transcription factor that probably corresponds to mammalian C/EBPbeta. Both types of binding sites were found to be required for full activity of the promoter. Remarkably, ectopic coexpression of Myb and NF-M proteins in erythroid cells or fibroblasts was sufficient to induce endogenous markers of myeloid differentiation, like the mim-1 and lysozyme genes. Our results indicate that c-Myb and NF-M proteins act as a bipartite, combinatorial signal that regulates the expression of myeloid-specific genes, even in heterologous cell types.
引用
收藏
页码:749 / 759
页数:11
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