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免疫球蛋白基因增强子中的蛋白质结合位点决定转录活性和诱导性。

Protein-binding sites in Ig gene enhancers determine transcriptional activity and inducibility.

作者信息

Lenardo M, Pierce J W, Baltimore D

出版信息

Science. 1987 Jun 19;236(4808):1573-7. doi: 10.1126/science.3109035.

DOI:10.1126/science.3109035
PMID:3109035
Abstract

Individual protein-binding sites within the mouse immunoglobulin heavy chain and kappa light chain gene enhancers were altered, making it possible to examine the functional role of the sites during transcription. The E motifs, which bind factors that are present in many if not all cells, mostly behave as transcriptional activating sites. The only known heavy chain enhancer site that binds a lymphocyte-specific factor, the "octamer" site, plays a critical role in transcription but only in a truncated form of the enhancer. In the full enhancer, no one site is crucial because of an apparent functional redundancy. The site in the kappa enhancer that binds a factor specific to mature B cells, kappa B, was crucial to the constitutive activity of the enhancer in B cells. This factor is also inducible in pre-B cells, and the site was necessary for inducibility of the kappa enhancer. Thus, the sites defined by protein binding are important for the functional activity of immunoglobulin enhancers, with the sites that bind proteins restricted in their cellular distribution playing the most important roles.

摘要

小鼠免疫球蛋白重链和κ轻链基因增强子内的各个蛋白质结合位点被改变,从而能够研究这些位点在转录过程中的功能作用。E基序可结合许多(即便不是所有)细胞中都存在的因子,大多表现为转录激活位点。唯一已知的能结合淋巴细胞特异性因子的重链增强子位点,即“八聚体”位点,在转录中起关键作用,但仅在增强子的截短形式中如此。在完整的增强子中,由于明显的功能冗余,没有一个位点是至关重要的。κ增强子中结合成熟B细胞特异性因子κB的位点,对增强子在B细胞中的组成型活性至关重要。该因子在前B细胞中也可被诱导,且该位点对于κ增强子的可诱导性是必需的。因此,由蛋白质结合所定义的位点对于免疫球蛋白增强子的功能活性很重要,其中结合细胞分布受限的蛋白质的位点发挥着最重要的作用。

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Protein-binding sites in Ig gene enhancers determine transcriptional activity and inducibility.免疫球蛋白基因增强子中的蛋白质结合位点决定转录活性和诱导性。
Science. 1987 Jun 19;236(4808):1573-7. doi: 10.1126/science.3109035.
2
A factor known to bind to endogenous Ig heavy chain enhancer only in lymphocytes is a ubiquitously active transcription factor.一种仅在淋巴细胞中与内源性免疫球蛋白重链增强子结合的因子是一种普遍活跃的转录因子。
Eur J Biochem. 1990 Feb 14;187(3):507-13. doi: 10.1111/j.1432-1033.1990.tb15332.x.
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Multiple nuclear factors interact with the immunoglobulin enhancer sequences.多种核因子与免疫球蛋白增强子序列相互作用。
Cell. 1986 Aug 29;46(5):705-16. doi: 10.1016/0092-8674(86)90346-6.
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Selective synergy of immunoglobulin enhancer elements in B-cell development: a characteristic of kappa light chain enhancers, but not heavy chain enhancers.免疫球蛋白增强子元件在B细胞发育中的选择性协同作用:κ轻链增强子的特征,而非重链增强子的特征。
Nucleic Acids Res. 1994 Oct 11;22(20):4216-23. doi: 10.1093/nar/22.20.4216.
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The effects of E mu, 3'alpha (hs 1,2) and 3'kappa enhancers on mutation of an Ig-VDJ-Cgamma2a Ig heavy gene in cultured B cells.Eμ、3'α(hs 1,2)和3'κ增强子对培养的B细胞中Ig-VDJ-Cγ2a Ig重链基因突变的影响。
Int Immunol. 1998 Aug;10(8):1121-9. doi: 10.1093/intimm/10.8.1121.
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A nuclear factor that binds to a conserved sequence motif in transcriptional control elements of immunoglobulin genes.一种与免疫球蛋白基因转录控制元件中的保守序列基序结合的核因子。
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Isolation of a candidate repressor/activator, NF-E1 (YY-1, delta), that binds to the immunoglobulin kappa 3' enhancer and the immunoglobulin heavy-chain mu E1 site.分离出一种候选阻遏物/激活物NF-E1(YY-1,δ),它能与免疫球蛋白κ轻链3'增强子及免疫球蛋白重链μ E1位点结合。
Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9804-8. doi: 10.1073/pnas.88.21.9804.
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Identification of an octamer-binding site in the mouse kappa light-chain immunoglobulin enhancer.小鼠κ轻链免疫球蛋白增强子中八聚体结合位点的鉴定。
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Using altered specificity Oct-1 and Oct-2 mutants to analyze the regulation of immunoglobulin gene transcription.利用特异性改变的Oct-1和Oct-2突变体分析免疫球蛋白基因转录的调控。
EMBO J. 1997 Dec 1;16(23):7105-17. doi: 10.1093/emboj/16.23.7105.
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J Immunol. 2000 Jan 15;164(2):795-804. doi: 10.4049/jimmunol.164.2.795.

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