Hes-1, a known transcriptional repressor, acts as a transcriptional activator for the human acid alpha-glucosidase gene in human fibroblast cells.
Hes-1, a known transcriptional repressor, acts as a transcriptional activator for the human acid alpha-glucosidase gene in human fibroblast cells.
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DOI：
10.1006/bbrc.2002.6483
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发表时间：
2002-03
影响因子：
3.1
通讯作者：
B. Yan;N. Raben;P. Plotz
中科院分区：
文献类型：
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作者：
B. Yan;N. Raben;P. Plotz
Hes-1是果蝇毛状蛋白和分裂蛋白增强子的哺乳动物同源物1，属于碱性螺旋-环-螺旋蛋白家族，其在神经发生、肌肉发生、造血和性别决定中是必需的。Hes-1是许多已知基因的转录抑制因子，包括我们先前在Hep G2细胞中显示的人酸性α-葡糖苷酶（GAA）基因。人GAA基因编码用于溶酶体中糖原分解的酶，其缺乏导致糖原累积病II型（庞贝氏综合征）。使用含有在Hep G2细胞和相同转录因子Hes-1和YY 1结合的条件下表现出抑制活性的DNA元件的构建体，我们已经表明该元件在人成纤维细胞中起增强子的作用。Hes-1的定点突变和过表达表明Hes-1具有转录激活因子的功能。我们已经发现Hes-1的双重功能可能有助于这种管家基因的微妙组织特异性控制。
Hes-1, the mammalian homologue 1 of Drosophila hairy and Enhancer of split proteins, belongs to a family of basic helix-loop-helix proteins that are essential to neurogenesis, myogenesis, hematopoiesis, and sex determination. Hes-1 is a transcriptional repressor for a number of known genes including the human acid alpha-glucosidase (GAA) gene as we have previously shown in Hep G2 cells. The human GAA gene encodes the enzyme for glycogen breakdown in lysosomes, deficiency of which results in Glycogen Storage Disease type II (Pompe syndrome). Using constructs containing the DNA element that demonstrates repressive activity in Hep G2 cells and conditions in which the same transcription factors, Hes-1 and YY1, bind, we have shown that this element functions as an enhancer in human fibroblasts. Site-directed mutagenesis and overexpression of Hes-1 showed that Hes-1 functions as a transcriptional activator. The dual function of Hes-1 we have found is likely to contribute to the subtle tissue-specific control of this housekeeping gene.