The carbonic anhydrase I locus contains a c-Myb target promoter and modulates differentiation of murine erythroleukemia cells.
The carbonic anhydrase I locus contains a c-Myb target promoter and modulates differentiation of murine erythroleukemia cells.
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碳酸酐酶 I 基因座含有 c-Myb 靶启动子并调节小鼠红白血病细胞的分化。
DOI：
10.1038/sj.onc.1209295
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Bender,TP
中科院分区：
文献类型：
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作者：
Chen,J;Kremer,CS;Bender,TP
Myb原癌基因编码正常造血所必需的转录因子（c-Myb），并且被认为通过调节特定靶基因的表达来调节造血细胞增殖和分化。我们确定小鼠红细胞特异性碳酸酐酶I启动子（CAIe）作为c-Myb活性的靶点，并证明Myb活性对C19 MEL细胞中碳酸酐酶I（CAI）的表达至关重要。当MEL细胞响应于MENT或用N，N-双乙酰胺（HMBA）处理而分化时，CAI表达下调。加塔-1与c-Myb的共表达导致来自CAIe启动子的转录的协同激活，并且两种转录因子在体内与CAIe启动子相互作用。我们鉴定了CAIe启动子中的新的20 bp序列，其足以介导c-Myb和加塔-1对CAIe启动子的协同激活。c-Myb和加塔-1与该DNA序列相互作用，表明c-Myb和加塔-1可能包含在与CAIe启动子的该区域相互作用的复合物中。CAI的强制表达延迟了HMBA诱导的MEL细胞分化，并使其保持在增殖状态。这些数据有力地表明CAI是c-Myb靶点，并且参与调节MEL细胞增殖和分化。
The Myb proto-oncogene encodes a transcription factor (c-Myb) that is essential for normal hematopoiesis and is thought to regulate hematopoietic cell proliferation and differentiation by regulating expression of specific target genes. We identify the mouse erythroid-specific carbonic anhydrase I promoter (CAIe) as a target of c-Myb activity and demonstrate that Myb activity is critical for carbonic anhydrase I (CAI) expression in C19 MEL cells. CAI expression is downregulated when MEL cells differentiate in response to MEnT or treatment with N, N-hexamethylene bisacetamide (HMBA). Coexpression of GATA-1 with c-Myb results in synergistic activation of transcription from the CAIe promoter and both transcription factors interact with the CAIe promoter in vivo. We identify a novel 20 bp sequence in the CAIe promoter that is sufficient to mediate synergistic activation of the CAIe promoter by c-Myb and GATA-1. c-Myb and GATA-1 interact with this DNA sequence suggesting that c-Myb and GATA-1 may be contained in a complex that interacts with this region of the CAIe promoter. Forced expression of CAI delayed HMBA-induced differentiation of MEL cells and maintained them in a proliferating state. These data strongly suggest that CAI is a c-Myb target and is involved in regulating MEL cell proliferation and differentiation.