Messier H, Brickner H, Gaikwad J, Fotedar A
Division of Molecular Biology, La Jolla Institute for Allergy and Immunology, California 92037.
Mol Cell Biol. 1993 Sep;13(9):5450-60. doi: 10.1128/mcb.13.9.5450-5460.1993.
POU domain proteins have been implicated in the regulation of a number of lineage-specific genes. Among the first POU domain proteins described were the immunoglobulin octamer-binding proteins Oct-1 and Oct-2. It was therefore of special interest when we identified a novel lymphoid POU domain protein in Southwestern (DNA-protein) screens of T-cell lambda gt11 libraries. This novel POU protein, TCF beta 1, binds in a sequence-specific manner to a critical motif in the T-cell receptor (TCR) beta enhancer. Sequence analysis revealed that TCF beta 1 represents a new class of POU domain proteins which are distantly related to other POU proteins. TCF beta 1 is encoded by multiple exons whose organization is distinct from that of other POU domain proteins. The expression of TCF beta 1 in a tissue-restricted manner and its ability to bind to multiple motifs in the TCR beta enhancer support a role in regulating TCR beta gene expression. The expression of TCF beta 1 in both B and T cells and the ability of recombinant TCF beta 1 to bind octamer and octamer-related motifs suggest that TCF beta 1 has additional roles in lymphoid cell function. The ability of TCF beta 1 to transactivate in a sequence-specific manner is consistent with a role for regulating lymphoid gene expression.
POU结构域蛋白与许多谱系特异性基因的调控有关。最早描述的POU结构域蛋白包括免疫球蛋白八聚体结合蛋白Oct-1和Oct-2。因此,当我们在T细胞λgt11文库的西南(DNA-蛋白质)筛选中鉴定出一种新型淋巴样POU结构域蛋白时,特别令人感兴趣。这种新型POU蛋白TCFβ1以序列特异性方式与T细胞受体(TCR)β增强子中的一个关键基序结合。序列分析表明,TCFβ1代表一类新的POU结构域蛋白,与其他POU蛋白有较远的亲缘关系。TCFβ1由多个外显子编码,其组织形式与其他POU结构域蛋白不同。TCFβ1在组织中以受限方式表达,并且能够与TCRβ增强子中的多个基序结合,这支持了它在调节TCRβ基因表达中的作用。TCFβ1在B细胞和T细胞中均有表达,重组TCFβ1能够结合八聚体和八聚体相关基序,这表明TCFβ1在淋巴细胞功能中还有其他作用。TCFβ1以序列特异性方式反式激活的能力与调节淋巴样基因表达的作用一致。