Transcriptional activation of the SALL1 by the human SIX1 homeodomain during kidney development
Transcriptional activation of the SALL1 by the human SIX1 homeodomain during kidney development
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DOI：
10.1074/jbc.m600180200
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发表时间：
2006-07-14
影响因子：
4.8
通讯作者：
Ma, Yupo
中科院分区：
文献类型：
--
作者：
Chai, Li;Yang, Jianchang;Ma, Yupo
SALL 1是SAL基因家族的成员，编码一组推定的发育转录因子。SALL 1在肾脏发育过程中起着关键作用，因为人类SALL 1基因的突变会导致与肾脏畸形相关的Townes-Brocks综合征。小鼠Sall 1基因的缺失导致肾发育不全或严重的发育不全。到目前为止，很少有人知道的分子机制控制SALL 1的表达调控。本报告描述了人SALL 1基因启动子的克隆和鉴定。鉴定了几种转录因子的共有结合位点，其中WT 1和SIX 1具有多个位点。在瞬时转染试验中，SALL 1启动子在HEK-293人肾细胞和COS-7猴肾细胞中的活性高于NIH-3 T3成纤维细胞，这与其在肾脏发育中的作用一致。SIX 1蛋白显著激活SALL 1启动子的转录。利用荧光素酶报告基因测定，内源或外源添加的SIX 1激活SALL 1启动子。SIX 1的过表达诱导内源性SIX 1蛋白的显著增加。此外，SIX 1和Eya 1的共表达导致SALL 1启动子活性的显着增加时，与SIX 1或Eya 1单独相比。最后，我们证明，SIX 1能够结合到SALL 1启动子的阻滞试验和删除的SIX 1推定的元素显着减少SALL 1启动子活性响应SIX 1刺激。我们的研究结果表明，SALL 1可能是肾脏发育过程中SIX 1的靶基因。
SALL1 is a member of the SAL gene family that encodes a group of putative developmental transcription factors. SALL1 plays a critical role during kidney development as mutations of the human SALL1 gene cause Townes-Brocks syndrome, which is associated with kidney malformation. Deletion of the mouse Sall1 gene results in renal agenesis or severe dysgenesis. To date, little is known about the molecular mechanisms controlling the regulation of SALL1 expression. This report describes the cloning and characterization of the human SALL1 gene promoter. Consensus binding sites were identified for several transcription factors, with multiple sites for WT1 and SIX1. In transient transfection assays, SALL1 promoter activity was higher in HEK-293 human kidney cells and COS-7 monkey kidney cells than in NIH-3T3 fibroblasts, consistent with its role in kidney development. Transcription from the SALL1 promoter was strikingly activated by the SIX1 protein. Utilizing a luciferase reporter gene assay, endogenous or exogenously added SIX1 activated the SALL1 promoter. Overexpression of SIX1 induced a significant increase in the endogenous SIX1 protein. In addition, co-expression of SIX1 and Eya1 resulted in a significant increase in the SALL1 promoter activity when compared with either SIX1 or Eya1 alone. Finally, we demonstrate that SIX1 was able to bind to the SALL1 promoter by retardation assays and that deletion of the putative element of SIX1 significantly diminishes the SALL1 promoter activity response to SIX1 stimulation. Our findings, when taken together, indicate that SALL1 is a likely target gene for SIX1 during kidney development.