A NUCLEAR FACTOR THAT BINDS TO A CONSERVED SEQUENCE MOTIF IN TRANSCRIPTIONAL CONTROL ELEMENTS OF IMMUNOGLOBULIN GENES
A NUCLEAR FACTOR THAT BINDS TO A CONSERVED SEQUENCE MOTIF IN TRANSCRIPTIONAL CONTROL ELEMENTS OF IMMUNOGLOBULIN GENES
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DOI：
10.1038/319154a0
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发表时间：
1986-01-09
期刊：
影响因子：
64.8
通讯作者：
SHARP, PA
中科院分区：
文献类型：
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作者：
SINGH, H;SEN, R;SHARP, PA
通过分析外源免疫球蛋白基因重组体在淋巴样细胞和非淋巴样细胞中的表达，推测了介导免疫球蛋白基因B细胞特异性转录的反式作用因子。已经确定了两个B细胞特异性的顺式作用转录调控元件。一个元件位于重链和κ轻链基因可变区(V)和恒定区(C)之间的内含子中，作为转录增强子1-6。第二个元件位于重链和κ轻链基因启动子的上游。该元件即使在病毒增强剂7-10存在的情况下也能指导淋巴特异性转录。我们通过应用改进的凝胶电泳法11-13寻找可能与这两个调节元件特异结合的核因子11-13。在这里，我们报告了一种人B细胞核因子A，它与小鼠Heavy和κ轻链基因启动子上游的DNA序列以及小鼠重链基因增强子的DNA序列结合。这种序列特异性结合可能是由高度保守的序列基序ATTTGCAT介导的，它存在于所有三个转录元件中。有趣的是，人类HeLa细胞中也存在一个与IgNF-A具有类似结合特异性的因子。
Trans-acting factors that mediate B-cell specific transcription of immunoglobulin genes have been postulated based on an analysis of the expression of exogenously introduced immunoglobulin gene recombinants in lymphoid and non-lymphoid cells. Two B-cell-specific,cis-acting transcriptional regulatory elements have been identified. One element is located in the intron between the variable (V) and constant (C) regions of both heavy and κ light-chain genes and acts as a transcriptional enhancer1–6. The second element is found upstream of both heavy and κ light-chain gene promoters. This element directs lymphoid-specific transcription even in the presence of viral enhancers7–10. We have sought nuclear factors that might bind specifically to these two regulatory elements by application of a modified gel electrophoresis DNA binding assay11–13. We report here the identification of a human B-cell nuclear factor (IgNF-A) that binds to DNA sequences in the upstream regions of both the mouse heavy and κ light-chain gene promoters and also to the mouse heavy-chain gene enhancer. This sequence-specific binding is probably mediated by a highly conserved sequence motif, ATTTGCAT, present in all three transcriptional elements. Interestingly, a factor showing similar binding specificity to IgNF-A is also present in human HeLa cells.