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小鼠髓系锌指蛋白2介导的髓系特异性转录激活

Myeloid-specific transcriptional activation by murine myeloid zinc-finger protein 2.

作者信息

Murai K, Murakami H, Nagata S

机构信息

Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565, Japan.

出版信息

Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3461-6. doi: 10.1073/pnas.95.7.3461.

Abstract

Myeloid zinc finger protein 2 (MZF-2) is a zinc-finger transcription factor that is expressed in myeloid cells, particularly in the cells committed to the neutrophilic lineage. Here we examine the ability of murine MZF-2 (mMZF-2) to activate transcription. The mMZF-2 protein binds to a DNA element (MZF-binding site) through its zinc-finger domain. When the intact mMZF-2 was cotransfected with a reporter gene, it did not activate transcription. However, N-terminal deletion mutants greatly enhanced transcription specifically in myeloid cells. Furthermore, in an in vivo competition assay, the middle region of MZF-2 inhibited the mMZF-2-mediated transcription activation. These results suggest that mMZF-2 is a transcriptional factor that can specifically work in myeloid cells and can be divided into at least three functional domains. The N-terminal domain inhibits transactivation by masking the effect of the activation domain. The middle region recruits a coactivator, which is responsible for myeloid-specific transcriptional activation. The C-terminal zinc-finger domain functions as a DNA-binding domain.

摘要

髓系锌指蛋白2(MZF - 2)是一种锌指转录因子,在髓系细胞中表达,尤其在定向于嗜中性粒细胞谱系的细胞中表达。在此,我们研究了小鼠MZF - 2(mMZF - 2)激活转录的能力。mMZF - 2蛋白通过其锌指结构域与一个DNA元件(MZF结合位点)结合。当完整的mMZF - 2与报告基因共转染时,它并未激活转录。然而,N端缺失突变体在髓系细胞中特异性地极大增强了转录。此外,在体内竞争试验中,MZF - 2的中间区域抑制了mMZF - 2介导的转录激活。这些结果表明,mMZF - 2是一种能在髓系细胞中特异性发挥作用的转录因子,并且可分为至少三个功能结构域。N端结构域通过掩盖激活结构域的作用来抑制反式激活。中间区域募集一个共激活因子,该共激活因子负责髓系特异性转录激活。C端锌指结构域作为DNA结合结构域发挥作用。

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