识别和描述一个守恒erythroid-specific增强器位于基因内区8人类5-aminolevulinate合酶2基因。
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考克斯TC, Surinya KH可能BK
识别和描述一个守恒erythroid-specific增强器位于基因内区8人类5-aminolevulinate合酶2基因。
J生物化学杂志。1998年7月3;273 (27):16798 - 809。
- PubMed ID
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9642238 (在PubMed]
- 文摘
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三十五个碱基的序列包括人类红细胞5-aminolevulinate合成酶基因(ALAS2)已经确定。分析显示GC含量很低,几乎没有重复的元素,和证据的插入reverse-transcribed信使rna序列和邻近基因。我们一直在调查内含子是否1、3和8,这对应于DNase I-hypersensitivity网站在老鼠ALAS2基因相关的结构,影响人类ALAS2启动子的表达瞬时表达检测。而内含子3略抑制性,人类基因的内含子1和8刺激启动子活动。基因内区8拥有强烈erythroid-specific增强剂orientation-dependent活动。删除分析该地区局部增强活动的239个碱基对的片段。转录因子结合位点集中在这个地区包括GATA图案和CACCC盒子,许多红细胞cell-expressed基因的关键调控序列。这些网站也在相应的小鼠和犬ALAS2基因的内含子。诱变的这些守恒的网站在人类基因内区8序列和红细胞细胞中瞬时表达分析建立了功能的重要性,一个叫主题和两个CACCC盒子。绑定GATA-1体外的叫图案。 The two functional CACCC boxes each bound Sp1 or a related protein in vitro, but binding of the erythroid Kruppel-like factor and the basic Kruppel-like factor could not be detected. The intron 8 enhancer region was not activated by GATA-1 together with Sp1 in transactivation experiments in COS-1 cells indicating the involvement of a related Sp1 protein or of another unidentified erythroid factor. Overall, these results demonstrate that a GATA-1-binding site and CACCC boxes located within the human ALAS2 intron 8 are critical for the erythroid-specific enhancer activity in transfected erythroid cells, and due to the conserved nature of these binding sites across species, it seems likely that these sites play a functional role in the tissue-restricted expression of the gene in vivo.