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一种新型锌指蛋白(HZF1)基因的鉴定、特征分析及其在K562细胞红系和巨核系分化中的功能

Identification and characterization of a novel zinc finger protein (HZF1) gene and its function in erythroid and megakaryocytic differentiation of K562 cells.

作者信息

Peng H, Du Z-W, Zhang J-W

机构信息

National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.

出版信息

Leukemia. 2006 Jun;20(6):1109-16. doi: 10.1038/sj.leu.2404212.

DOI:10.1038/sj.leu.2404212
PMID:16628192
Abstract

A novel zinc finger protein (HZF1) gene was identified and characterized by screening a human bone marrow cDNA library, using a new expression sequence tag probe that contains sequences encoding zinc finger motifs. There are at least three transcripts that may result from different splicing of the pre-mRNA, but the differences among them are only involved in 5' non-translation region of HZF1 mRNA. HZF1 gene contains four exons and three introns. The putative protein consists of 670 amino-acid residues including 15 typical C2H2 and 2 C2RH zinc finger motifs. This structure characterization of HZF1 and the nuclear location of the protein suggest that HZF1 may function as a transcription factor. HZF1 mRNA expression was detected in ubiquitous tissues and various hematopoietic cell lines. Increased HZF1 mRNA expression was observed following erythroid differentiation of K562 cells induced by hemin or megakaryocytic differentiation of K562 cells induced by phorbol myristate acetate (PMA). Both of the antisense method and RNA interference assay revealed that repression of the intrinsic expression of HZF1 blocked the hemin-induced erythroid differentiation and reduced the PMA-induced megakaryocytic differentiation of K562 cells, which suggested that HZF1 play important roles in erythroid and megakaryocytic differentiation.

摘要

通过使用包含编码锌指基序序列的新表达序列标签探针筛选人骨髓cDNA文库,鉴定并表征了一种新型锌指蛋白(HZF1)基因。前体mRNA的不同剪接可能产生至少三种转录本,但它们之间的差异仅涉及HZF1 mRNA的5'非翻译区。HZF1基因包含四个外显子和三个内含子。推定的蛋白质由670个氨基酸残基组成,包括15个典型的C2H2和2个C2RH锌指基序。HZF1的这种结构特征以及该蛋白的核定位表明HZF1可能作为转录因子发挥作用。在普遍存在的组织和各种造血细胞系中检测到HZF1 mRNA表达。在氯化血红素诱导K562细胞向红系分化或佛波酯(PMA)诱导K562细胞向巨核系分化后,观察到HZF1 mRNA表达增加。反义方法和RNA干扰试验均表明,抑制HZF1的内在表达可阻断氯化血红素诱导的K562细胞红系分化,并降低PMA诱导的K562细胞巨核系分化,这表明HZF1在红系和巨核系分化中起重要作用。

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