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首页> 外文期刊>Molecular and Cellular Biology >The SCL +40 Enhancer Targets the Midbrain Together with Primitive and Definitive Hematopoiesis and Is Regulated by SCL and GATA Proteins
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The SCL +40 Enhancer Targets the Midbrain Together with Primitive and Definitive Hematopoiesis and Is Regulated by SCL and GATA Proteins

机译：SCL +40增强剂靶向中脑以及原始和确定性造血功能，并受SCL和GATA蛋白调控

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The SCL/Tal-1 gene encodes a basic helix-loop-helix transcription factor with key roles in hematopoietic and neural development. SCL is expressed in, and required for, both primitive and definitive erythropoiesis. Thus far, we have identified only one erythroid SCL enhancer. Located 40 kb downstream of exon 1a, the +40 enhancer displays activity in primitive erythroblasts. We demonstrate here that a 3.7-kb fragment containing this element also targets expression to the midbrain, a known site of endogenous SCL expression. Although the 3.7-kb construct was active in primitive, but not definitive, erythroblasts, a larger 5.0-kb fragment, encompassing the 3.7-kb region, was active in both fetal and adult definitive hematopoietic cells. This included Ter119+ erythroid cells along with fetal liver erythroid and myeloid progenitors. Unlike two other SCL hematopoietic enhancers (+18/19 and ?4), +40 enhancer transgenes were inactive in the endothelium. A conserved 400-bp core region, essential for both hematopoietic and midbrain +40 enhancer activity in embryos, relied on two GATA/E-box motifs and was bound in vivo by GATA-1 and SCL in erythroid cells. These results suggest a model in which the SCL +18/19 and/or ?4 enhancers initiate SCL expression in early mesodermal derivatives capable of generating blood and endothelium, with subsequent activation of the +40 enhancer via an autoregulatory loop.
机译： SCL / Tal-1 基因编码基本的螺旋-环-螺旋转录因子，在造血和神经发育中起关键作用。 SCL在原始和确定性红细胞生成中都表达并且是必需的。到目前为止，我们只鉴定了一种类红细胞 SCL 增强子。 +40增强子位于外显子1a下游40 kb，在原始成红细胞中显示活性。在这里，我们证明了一个3.7kb的片段，其中包含该元素也将表达靶向中脑，即内源性SCL表达的已知位点。尽管3.7kb的构建体在原始的但非确定性的细胞中有活性，但成血红细胞，一个较大的5.0kb的片段（包含3.7kb的区域）在胎儿和成年的造血细胞中都具有活性。其中包括Ter119 + 红细胞，以及胎儿肝红细胞和髓样祖细胞。与其他两种 SCL 造血增强子（+18/19和？4）不同，+ 40增强子转基因在内皮细胞中没有活性。一个保守的400 bp核心区域，对胚胎的造血和中脑+40增强子活性都是必不可少的，它依赖于两个GATA / E-box模体，并在体内被GATA-1和SCL结合在类红细胞中。这些结果表明了一个模型，其中 SCL +18/19和/或？4增强子在能够产生血液和内皮的早期中胚层衍生物中启动 SCL 表达，并随后激活+40增强子通过一个自动调节回路。

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