LEF-1, A GENE ENCODING A LYMPHOID-SPECIFIC WITH PROTEIN, AN HMG DOMAIN, REGULATES T-CELL RECEPTOR-ALPHA ENHANCER FUNCTION
LEF-1, A GENE ENCODING A LYMPHOID-SPECIFIC WITH PROTEIN, AN HMG DOMAIN, REGULATES T-CELL RECEPTOR-ALPHA ENHANCER FUNCTION
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DOI：
10.1101/gad.5.5.880
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发表时间：
1991-05-01
影响因子：
10.5
通讯作者：
GROSSCHEDL, R
中科院分区：
文献类型：
--
作者：
TRAVIS, A;AMSTERDAM, A;GROSSCHEDL, R
分离出了淋巴细胞特异性的cDNA克隆，它们编码一种核蛋白，该蛋白与染色体非组蛋白HMG - 1以及细胞特化的假定调节因子具有同源性，这些调节因子包括哺乳动物的睾丸决定因子SRY和真菌的交配型蛋白。由分离的cDNA克隆所代表的基因被称为LEF - 1（淋巴细胞增强子结合因子1），它受到发育调控，在前B淋巴细胞和T淋巴细胞中表达，但在后期的B细胞或非淋巴细胞组织中不表达。内源性和重组的LEF - 1都被证明能与T细胞抗原受体（TCR）α增强子中一个具有重要功能的位点结合。发现TCR - α增强子的最大活性与LEF - 1的细胞类型特异性表达模式相符。此外，在后期B细胞中强制表达重组LEF - 1会增强TCR - α增强子的功能。综上所述，这些数据表明LEF - 1是淋巴细胞基因表达和分化的一种调节参与者。
Lymphoid-specific cDNA clones were isolated that encode a nuclear protein with homology to the chromosomal nonhistone protein HMG-1 and to putative regulators of cell specialization, including the mammalian testis-determining factor SRY and fungal mating-type proteins. The gene represented by the isolated cDNA clones, termed LEF-1 (lymphoid enhancer-binding factor 1), is developmentally regulated and expressed in pre-B and T lymphocytes but not in later-stage B cells or nonlymphoid tissues. Both endogenous and recombinant LEF-1 were shown to bind to a functionally important site in the T-cell antigen receptor (TCR) alpha-enhancer. Maximal TCR-alpha enhancer activity was found to parallel the cell type-specific expression pattern of LEF-1. Moreover, forced expression of recombinant LEF-1 in late stage B cells increases TCR-alpha enhancer function. Taken together, these data suggest that LEF-1 is a regulatory participant in lymphocyte gene expression and differentiation.