GLIS3, a novel member of the GLIS subfamily of Kruppel-like zinc finger proteins with repressor and activation functions
GLIS3, a novel member of the GLIS subfamily of Kruppel-like zinc finger proteins with repressor and activation functions
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DOI：
10.1093/nar/gkg776
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发表时间：
2003-10-01
影响因子：
14.9
通讯作者：
Jetten, AM
中科院分区：
文献类型：
--
作者：
Kim, YS;Nakanishi, G;Jetten, AM
在这项研究中，我们描述了一个新的转录因子GLI-类似3（GLIS 3）的鉴定和表征。GLIS 3是一个分子量为83.8 kDa的核蛋白，含有5个C2 H2型Kruppel样锌指结构域，与GLIS 1的锌指结构域具有93%的同源性，但在锌指结构域之外几乎没有同源性。GLIS 3可以作为转录的抑制因子和激活因子发挥作用。缺失突变体分析确定N-和C-末端是最佳转录活性所需的。GLIS 3与GLI-RE共有序列结合并能够增强GLI-RE依赖性转录。GLIS 3（DeltaC 496）是一种显性负突变体，可抑制GLIS 3和GLI 1的转录激活。对E6.5至E14.5期小鼠胚胎的整体原位杂交表明，GLIS 3在发育中的肾脏和睾丸的特定区域表达，并且在神经形成期间以高度动态的模式表达。从E11.5到E12.5，GLIS 3在趾间区强烈表达，该趾间区注定要经历凋亡。在胚胎发育过程中观察到的GLIS 3表达的时间和空间模式表明，它可能在发育过程中的各种细胞过程的调节中发挥关键作用。GLIS 3的抑制和激活功能都可能参与这种调控。
In this study, we describe the identification and characterization of a novel transcription factor GLI-similar 3 (GLIS3). GLIS3 is an 83.8 kDa nuclear protein containing five C2H2-type Kruppel-like zinc finger motifs that exhibit 93% identity with those of GLIS1, however, little homology exists outside their zinc finger domains. GLIS3 can function as a repressor and activator of transcription. Deletion mutant analysis determined that the N- and C-termini are required for optimal transcriptional activity. GLIS3 binds to the GLI-RE consensus sequence and is able to enhance GLI-RE-dependent transcription. GLIS3(DeltaC496), a dominant-negative mutant, inhibits transcriptional activation by GLIS3 and GLI1. Whole mount in situ hybridization on mouse embryos from stage E6.5 through E14.5 demonstrated that GLIS3 is expressed in specific regions in developing kidney and testis and in a highly dynamic pattern during neurulation. From E11.5 through E12.5 GLIS3 was strongly expressed in the interdigital regions, which are fated to undergo apoptosis. The temporal and spatial pattern of GLIS3 expression observed during embryonic development suggests that it may play a critical role in the regulation of a variety of cellular processes during development. Both the repressor and activation functions of GLIS3 may be involved in this control.