Transcriptional regulation of the stem cell leukemia gene by PU.1 and Elf-1
Transcriptional regulation of the stem cell leukemia gene by PU.1 and Elf-1
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DOI：
10.1074/jbc.273.44.29032
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发表时间：
1998-10-30
影响因子：
4.8
通讯作者：
Green, AR
中科院分区：
文献类型：
--
作者：
Bockamp, EO;Fordham, JL;Green, AR
SCL基因，也称为tal-1，编码一种基本的螺旋-环-螺旋转录因子，对所有造血谱系的正常发育至关重要。SCL在定向红细胞、肥大细胞和巨核细胞以及造血干细胞中表达。对于肥大细胞中SCL转录的调节还不清楚，在其他谱系中，加塔-1是唯一被识别为调节SCL基因的组织特异性转录因子。因此，我们分析了肥大细胞SCL表达的分子机制。在本文中，我们证明了SCL启动子la与Spl和Sp3一起以类似于红系细胞中的情况的方式被加塔-1调节。然而，SCL启动子Ib在肥大细胞中具有强烈的活性，与红系细胞中的情况形成鲜明对比。启动子Ib的完全活性依赖于ETS和Sp1/3基序。转录因子PU.1、Elf-1、Sp1和Sp3都存在于肥大细胞提取物中，与启动子Ib和反式激活的启动子Ib报告构建体结合。这些数据首次证明SCL基因是PU.1、Elf-1和Sp3的直接靶点。
The SCL gene, also known as tal-1, encodes a basic helix-loop-helix transcription factor that is pivotal for the normal development of all hematopoietic lineages. SCL is expressed in committed erythroid, mast, and megakaryocytic cells as well as in hematopoietic stem cells. Nothing is known about the regulation of SCL transcription in mast cells, and in other lineages GATA-1 is the only tissue-specific transcription factor recognized to regulate the SCL gene. We have therefore analyzed the molecular mechanisms underlying SCL expression in mast cells. In this paper, we demonstrate that SCL promoter la was regulated by GATA-1 together with Spl and Sp3 in a manner similar to the situation in erythroid cells. However, SCL promoter Ib was strongly active in mast cells, in marked contrast to the situation in erythroid cells. Full activity of promoter Ib was dependent on ETS and Sp1/3 motifs, Transcription factors PU.1, Elf-1, Spl, and Sp3 were all present in mast cell extracts, bound to promoter Ib and transactivated promoter Ib reporter constructs. These data provide the first evidence that the SCL gene is a direct target for PU.1, Elf-1, and Sp3.