Bockamp E O, Fordham J L, Göttgens B, Murrell A M, Sanchez M J, Green A R
University of Cambridge, Department of Haematology, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, United Kingdom.
J Biol Chem. 1998 Oct 30;273(44):29032-42. doi: 10.1074/jbc.273.44.29032.
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 1a was regulated by GATA-1 together with Sp1 and Sp3 in a manner similar to the situation in erythroid cells. However, SCL promoter 1b was strongly active in mast cells, in marked contrast to the situation in erythroid cells. Full activity of promoter 1b was dependent on ETS and Sp1/3 motifs. Transcription factors PU.1, Elf-1, Sp1, and Sp3 were all present in mast cell extracts, bound to promoter 1b and transactivated promoter 1b reporter constructs. These data provide the first evidence that the SCL gene is a direct target for PU.1, Elf-1, and Sp3.
SCL基因，也被称为tal-1，编码一种基本的螺旋-环-螺旋转录因子，该因子对于所有造血谱系的正常发育至关重要。SCL在定向分化的红细胞、肥大细胞和巨核细胞以及造血干细胞中表达。关于肥大细胞中SCL转录的调控尚无相关信息，在其他谱系中，GATA-1是唯一已知的调控SCL基因的组织特异性转录因子。因此，我们分析了肥大细胞中SCL表达的分子机制。在本文中，我们证明SCL启动子1a受GATA-1以及Sp1和Sp3的调控，其方式与红细胞中的情况类似。然而，SCL启动子1b在肥大细胞中具有很强的活性，这与红细胞中的情况形成显著对比。启动子1b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均存在于肥大细胞提取物中，与启动子1b结合并激活启动子1b报告基因构建体。这些数据首次证明SCL基因是PU.1、Elf-1和Sp3的直接靶标。
