Early hematopoietic zinc finger protein (EHZF), the human homolog to mouse Evi3, is highly expressed in primitive human hematopoietic cells
Early hematopoietic zinc finger protein (EHZF), the human homolog to mouse Evi3, is highly expressed in primitive human hematopoietic cells
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DOI：
10.1182/blood-2003-07-2388
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发表时间：
2004-03-15
期刊：
影响因子：
20.3
通讯作者：
Venuta, S
中科院分区：
文献类型：
--
作者：
Bond, HM;Mesuraca, M;Venuta, S
通过比较人造血祖细胞和成熟白细胞的基因表达谱，鉴定出在CD34(+)细胞中表达的转录本，而在分化的细胞中检测不到。对该基因进行测序(命名为EHZF：早期造血锌指)，发现30个锌指与小鼠Evi3有96%的同源性，Evi3是最近发现的与AKXD-27 B细胞淋巴瘤逆转录病毒整合位点相关的基因。EHZF和Evi3与转录辅助因子OAZ有很高的同源性，参与了嗅觉上皮和B淋巴细胞分化的调控以及骨形态发生蛋白(BMP)的信号转导。我们发现：(1)EHZF在人CD34+祖细胞中大量表达，并且在细胞因子驱动的分化过程中迅速下降；(2)在大多数急性髓系白血病中发现了显著的mRNA水平；(3)EHZF复合体Smads 1和4与BMP2/4反应元件结合并增强其转录活性；(4)EHZF抑制早期B细胞因子(EBF)的转录活性，EBF是指定B细胞谱系所必需的转录因子。综上所述，我们的数据表明，EHZF可能在人类造血调控中发挥相关作用，并可能与血液系统恶性肿瘤的发生有关。(C)2004年，由美国血液病学会提供。
Comparison of the gene expression repertoire in human hematopoietic progenitors and mature leukocytes led to identification of a transcript expressed in CD34(+) cells and undetectable in differentiated cells. Sequencing of the cDNA (termed EHZF: early hematopoietic zinc finger) revealed 30 zinc fingers with 96% homology to mouse Evi3, a recently identified gene associated with the retroviral integration site in AKXD-27 B-cell lymphomas. EHZF and Evi3 share high homology with the transcription cofactor OAZ, implicated in the control of olfactory epithelium and B-lymphocyte differentiation and in the bone morphogenic protein (BMP) signal transduction. Here we show that (1) EHZF expression is abundant in human CD34+ progenitors and declines rapidly during cytokine-driven differentiation; (2) significant mRNA levels are found in most acute myelogenous leukemias; (3) in response to BMPs EHZF complexes SMADs 1 and 4, binds to, and enhances the transcriptional activity of, a BMP2/4 responsive element; (4) EHZF inhibits the transcriptional activity of early B-cell factor (EBF), a transcription factor essential for specification of the B-cell lineage. Taken together, our data suggest that EHZF is likely to play a relevant role in the control of human hematopoiesis and might be implicated in the development of hematopoietic malignancies. (C) 2004 by The American Society of Hematology.