All known in vivo functions of the Oct-2 transcription factor require the C-terminal protein domain
All known in vivo functions of the Oct-2 transcription factor require the C-terminal protein domain
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DOI：
10.4049/jimmunol.172.5.2962
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发表时间：
2004-03-01
影响因子：
4.4
通讯作者：
Humbert, PO
中科院分区：
文献类型：
--
作者：
Corcoran, LM;Koentgen, F;Humbert, PO
Oct-2是一种在B淋巴细胞谱系和发育中的CNS中表达的转录因子，通过许多离散的蛋白质结构域发挥功能。这些包括DNA结合POU同源结构域，两侧是两个转录激活结构域。体外研究表明，C-末端激活结构域，一个富含丝氨酸、苏氨酸和脯氨酸的序列，具有独特的性质，包括以B细胞特异性方式从远处激活转录的能力。在这项研究中，我们描述了小鼠的内源性oct-2基因已被修改，通过基因靶向创建一个突变的等位基因，oct-2DeltaC，它编码的Oct-2蛋白亚型，缺乏所有序列的DNA结合结构域的C-末端。令人惊讶的是，尽管保留了DNA结合结构域和富含谷氨酰胺的N-末端活化结构域，但由oct-2DeltaC等位基因编码的截短蛋白不能挽救任何先前描述的由oct-2缺失小鼠表现出的缺陷。纯合子oct-2 DeltaC/DeltaC小鼠出生后不久死亡，B细胞成熟、B-1细胞自我更新、血清IG水平和对体外刺激的B淋巴细胞应答均降低或不存在，其程度等同于在oct-2缺失小鼠中观察到的。我们的结论是，C-末端激活域的Oct-2是必需的，以介导独特的和不可缺少的功能的Oct-2转录因子在体内。
Oct-2, a transcription factor expressed in the B lymphocyte lineage and in the developing CNS, functions through of a number of discrete protein domains. These include a DNA-binding POU homeodomain flanked by two transcriptional activation domains. In vitro studies have shown that the C-terminal activation domain, a serine-, threonine- and proline-rich sequence, possesses unique qualities, including the ability to activate transcription from a distance in a B cell-specific manner. In this study, we describe mice in which the endogenous oct-2 gene has been modified through gene targeting to create a mutated allele, oct-2DeltaC, which encodes Oct-2 protein isoforms that lack all sequence C-terminal to the DNA-binding domain. Surprisingly, despite the retention of the DNA-binding domain and the glutamine-rich N-terminal activation domain, the truncated protein(s) encoded by the oct-2DeltaC allele are unable to rescue any of the previously described defects exhibited by oct-2 null mice. Homozygous oct-2DeltaC/DeltaC mice die shortly after birth, and B cell maturation, B-1 cell self renewal, serum Ig levels, and B lymphocyte responses to in vitro stimulation are all reduced or absent, to a degree equivalent to that seen in oct-2 null mice. We conclude that the C-terminal activation domain of Oct-2 is required to mediate the unique and indispensable functions of the Oct-2 transcription factor in vivo.