CBF alpha3 (AML2) is induced by TGF-beta1 to bind and activate the mouse germline Ig alpha promoter.
CBF alpha3 (AML2) is induced by TGF-beta1 to bind and activate the mouse germline Ig alpha promoter.
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发表时间：
1998-12
影响因子：
4.4
通讯作者：
M. Shi;J. Stavnezer
中科院分区：
文献类型：
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作者：
M. Shi;J. Stavnezer
TGF-β 1通过诱导生殖系（GL）IG α转录物，指导脾B细胞和表面IgM+ B细胞系I.29 μ向伊加的类别转换。相对于小鼠GL α转录物的第一起始位点，-130和+46之间的启动子片段足以在B细胞系中表达和TGF-β 1诱导报告基因。在该片段内存在TGF-β 1-应答元件（TbetaRE），其是TGF-β 1诱导启动子所需的，并且当多聚化时，足以将TGF-β 1诱导转移到另一个启动子。在这份报告中，我们表明，TGF-β 1诱导复合物结合TbetaRE，并包含转录因子核心结合因子（CBF;也称为急性髓性白血病，AML）。尽管所有三个CBF α家族成员都激活GL α启动子，但在脾B和I.29 μ细胞中，只有CBF α 3（AML-2）被TGF-β 1诱导。TbetaRE含有两个CBF结合位点。这两个位点的突变减少但不消除TGF-β 1或CBF过表达对GL α启动子的诱导，这可能是由于启动子中存在额外的CBF位点。此外，TbetaRE含有另一个序列基序的两个拷贝。这些基序的突变消除了GL α启动子的TGF-β 1诱导。总之，这些数据表明TGF-β 1对α启动子的诱导涉及CBF α 3的诱导，CBF α 3与一种或多种蛋白质沿着结合启动子的T β RE。
TGF-beta1 directs class switching to IgA by splenic B cells and by the surface IgM+ B cell line, I.29mu, by inducing germline (GL) Ig alpha transcripts. The promoter segment between -130 and +46, relative to the first initiation site for mouse GL alpha transcripts, is sufficient for expression and TGF-beta1 inducibility of a reporter gene in B cell lines. Within this segment resides a TGF-beta1-responsive element (TbetaRE) that is required for induction of the promoter by TGF-beta1 and, when multimerized, is sufficient to transfer TGF-beta1 inducibility to another promoter. In this report we show that a TGF-beta1-inducible complex binds the TbetaRE and contains the transcription factor core-binding factor (CBF; also known as acute myeloid leukemia, AML). Although all three CBF alpha family members activate the GL alpha promoter, only CBF alpha3 (AML-2) is induced by TGF-beta1 in splenic B and I.29mu cells. The TbetaRE contains two CBF binding sites. Mutation of both sites reduces but does not eliminate induction of the GL alpha promoter by TGF-beta1 or by overexpression of CBF, possibly due to the presence of an additional CBF site in the promoter. In addition, the TbetaRE contains two copies of another sequence motif. Mutation of these motifs eliminates TGF-beta1 induction of the GL alpha promoter. Together the data indicate that TGF-beta1 induction of the alpha promoter involves induction of CBF alpha3, which binds to the TbetaRE of the promoter along with one or more proteins.