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鸡GATA-2基因在造血祖细胞中的交替启动子与表达的发育调控

Alternate promoters and developmental modulation of expression of the chicken GATA-2 gene in hematopoietic progenitor cells.

作者信息

Nony P, Hannon R, Gould H, Felsenfeld G

机构信息

Laboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-0540, USA.

出版信息

J Biol Chem. 1998 Dec 4;273(49):32910-9. doi: 10.1074/jbc.273.49.32910.

Abstract

We have isolated and characterized the chicken GATA-2 (cGATA-2) gene. We show that, as in the case of some other members of the GATA gene family, the gene is expressed from alternative first exons. One of the resulting mRNAs represents only a minor form of the GATA-2 mRNA in the cells and tissues we analyzed; the other is ubiquitously expressed. We have defined the minimal promoter that controls expression of this most abundant mRNA and that is necessary for full activity in hematopoietic progenitor cells. The activity of this promoter in transient assays is consistent with developmental differences of expression levels in these cells. We identify within the promoter a previously unrecognized extended CCAAT motif essential for its activity. The organization of the cGATA-2 gene, with alternative first exons and a CCAAT box in the proximal promoter, is similar to that recently described for mouse GATA-2, and the proximal promoter also resembles the only promoter so far described in Xenopus. Nonetheless, the roles of the promoters in development and tissue-specific expression are quite different in these organisms, most strikingly in the mouse, which assigns developmental roles to its proximal and distal promoters that are quite different from those in the chicken. We suggest that although the overall organization may remain the same, the role assigned to each promoter varies among organisms. We identify distant upstream regulatory elements in the cGATA-2 gene that modulate expression from the proximal promoter and that may be responsible for this variation.

摘要

我们已经分离并鉴定了鸡GATA-2(cGATA-2)基因。我们发现,与GATA基因家族的其他一些成员一样,该基因由不同的首个外显子表达。在我们分析的细胞和组织中,其中一种产生的mRNA仅代表GATA-2 mRNA的次要形式;另一种则广泛表达。我们已经确定了控制这种最丰富mRNA表达的最小启动子,它对于造血祖细胞的充分活性是必需的。该启动子在瞬时分析中的活性与这些细胞中表达水平的发育差异一致。我们在启动子内鉴定出一个以前未被识别的扩展CCAAT基序,它对其活性至关重要。cGATA-2基因的结构,具有不同的首个外显子和近端启动子中的CCAAT框,与最近描述的小鼠GATA-2相似,近端启动子也类似于迄今为止在非洲爪蟾中描述的唯一启动子。尽管如此,这些生物体中启动子在发育和组织特异性表达中的作用却大不相同,在小鼠中最为明显,小鼠赋予其近端和远端启动子的发育作用与鸡中的截然不同。我们认为,尽管总体结构可能保持不变,但每个启动子所赋予的作用在不同生物体中有所不同。我们在cGATA-2基因中鉴定出远距离上游调控元件,它们调节近端启动子的表达,可能是造成这种差异的原因。

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