Wirth T, Priess A, Annweiler A, Zwilling S, Oeler B
Zentrum für Molekulare Biologie, Universität Heidelberg (ZMBH), FRG.
Nucleic Acids Res. 1991 Jan 11;19(1):43-51. doi: 10.1093/nar/19.1.43.
The interaction of the Oct2 transcription factor with the cognate octamer motif ATGCAAAT is a critical determinant of the lymphoid-specific expression of immunoglobulin genes. Ectopic expression of cloned Oct2 cDNA was shown to be sufficient to reconstitute at least some aspects of this regulation in non-lymphoid cells. We describe the isolation and characterization of multiple cDNAs encoding mouse Oct2 from a mature B-cell line and we show that a variety of isoforms of this transcription factor is generated from a single gene by an alternative splicing mechanism. All the isoforms retain the previously characterized POU-domain and are therefore able to bind to the octamer motif. Different amounts of the various isoforms are present within the same B-cell regardless of the developmental stage of B-cell differentiation and at least some of the isoforms are conserved between mouse and humans. In cotransfection experiments we show that all the isoforms are able to activate an octamer containing promoter element in fibroblasts revealing an unexpected functional redundancy. Finally, we show that one of the isoforms encodes the previously described lymphoid-specific Oct2B protein which has been suggested to be involved in the function of the octamer motif in the context of the immunoglobulin heavy-chain (IgH) enhancer.
Oct2转录因子与同源八聚体基序ATGCAAAT的相互作用是免疫球蛋白基因淋巴特异性表达的关键决定因素。已证明克隆的Oct2 cDNA的异位表达足以在非淋巴细胞中重建这种调控的至少某些方面。我们描述了从成熟B细胞系中分离和鉴定多个编码小鼠Oct2的cDNA，并表明该转录因子的多种同工型是通过可变剪接机制从单个基因产生的。所有同工型都保留了先前表征的POU结构域，因此能够结合八聚体基序。无论B细胞分化的发育阶段如何，同一B细胞内都存在不同数量的各种同工型，并且至少某些同工型在小鼠和人类之间是保守的。在共转染实验中，我们表明所有同工型都能够激活成纤维细胞中含八聚体的启动子元件，揭示了意想不到的功能冗余。最后，我们表明其中一种同工型编码先前描述的淋巴特异性Oct2B蛋白，有人认为该蛋白在免疫球蛋白重链（IgH）增强子的背景下参与八聚体基序的功能。
