TBP2 is essential for germ cell development by regulating transcription and chromatin condensation in the oocyte
TBP2 is essential for germ cell development by regulating transcription and chromatin condensation in the oocyte
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DOI：
10.1101/gad.535209
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发表时间：
2009-09-15
影响因子：
10.5
通讯作者：
Torres-Padilla, Maria-Elena
中科院分区：
文献类型：
--
作者：
Gazdag, Emese;Santenard, Angele;Torres-Padilla, Maria-Elena
生殖系的发育需要连续的分化事件。这些调节与生殖细胞特异性和多能性相关的转录因子有关，但一般转录因子（GTFs）的作用仍然难以捉摸。塔塔结合蛋白（tata binding protein， TBP）是一种参与所有RNA聚合酶转录的GTF。在小鼠卵巢卵泡形成过程中，TBP家族的脊椎动物特异性成员TBP2/TRF3仅在卵母细胞中表达。为了确定TBP2在体内的功能，我们制造了TBP2缺陷小鼠。我们发现Tbp2（-/-）小鼠是活的，没有明显的表型。然而，缺乏TBP2的雌性由于卵泡发育缺陷、染色质组织改变和关键卵母细胞特异性基因的转录失调而不育。TBP2与失调基因的启动子结合，表明TBP2直接调控其表达。相比之下，TBP消融在女性生殖系导致正常排卵和受精，表明在这些细胞中TBP是可有可无的。我们证明了TBP2对雌性生殖细胞的分化至关重要，并在小鼠中展示了TBP和TBP2这两个关键的核心启动子结合因子的互斥功能。
Development of the germline requires consecutive differentiation events. Regulation of these has been associated with germ cell-specific and pluripotency-associated transcription factors, but the role of general transcription factors (GTFs) remains elusive. TATA-binding protein (TBP) is a GTF involved in transcription by all RNA polymerases. During ovarian folliculogenesis in mice the vertebrate-specific member of the TBP family, TBP2/TRF3, is expressed exclusively in oocytes. To determine TBP2 function in vivo, we generated TBP2-deficient mice. We found that Tbp2(-/-) mice are viable with no apparent phenotype. However, females lacking TBP2 are sterile due to defective folliculogenesis, altered chromatin organization, and transcriptional misregulation of key oocyte-specific genes. TBP2 binds to promoters of misregulated genes, suggesting that TBP2 directly regulates their expression. In contrast, TBP ablation in the female germline results in normal ovulation and fertilization, indicating that in these cells TBP is dispensable. We demonstrate that TBP2 is essential for the differentiation of female germ cells, and show the mutually exclusive functions of these key core promoter-binding factors, TBP and TBP2, in the mouse.