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首页> 外文期刊>Molecular and Cellular Biology >Fbx15 Is a Novel Target of Oct3/4 but Is Dispensable for Embryonic Stem Cell Self-Renewal and Mouse Development
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Fbx15 Is a Novel Target of Oct3/4 but Is Dispensable for Embryonic Stem Cell Self-Renewal and Mouse Development

机译：Fbx15是Oct3 / 4的新型目标，但对于胚胎干细胞的自我更新和小鼠发育是必不可少的

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Embryonic stem (ES) cells are immortal and pluripotent cells derived from early mammalian embryos. Transcription factor Oct3/4 is essential for self-renewal of ES cells and early mouse development. However, only a few Oct3/4 target genes have been identified. In this study, we found that F-box-containing protein Fbx15 was expressed predominantly in mouse undifferentiated ES cells. Inactivation of Oct3/4 in ES cells led to rapid extinction of Fbx15 expression. Reporter gene analyses demonstrated that this ES cell-specific expression required an 18-bp enhancer element located approximately 500 nucleotides upstream from the transcription initiation site. The enhancer contained an octamer-like motif and an adjacent Sox-binding motif. Deletion or point mutation of either motif abolished the enhancer activity. The 18-bp fragment became active in NIH 3T3 cells when Oct3/4 and Sox2 were coexpressed. A gel mobility shift assay demonstrated cooperative binding of Oct3/4 and Sox2 to the enhancer sequence. In mice having a β-galactosidase gene knocked into the Fbx15 locus, 5-bromo-4-chloro-3-indolyl-β-d-galactopyranoside staining was detected in ES cells, early embryos (two-cell to blastocyst stages), and testis tissue. Despite such specific expression of Fbx15, homozygous mutant mice showed no gross developmental defects and were fertile. Fbx15-null ES cells were normal in morphology, proliferation, and differentiation. These data demonstrate that Fbx15 is a novel target of Oct3/4 but is dispensable for ES cell self-renewal, development, and fertility.
机译：胚胎干（ES）细胞是源自早期哺乳动物胚胎的永生和多能细胞。转录因子Oct3 / 4对于ES细胞的自我更新和小鼠早期发育至关重要。然而，仅鉴定了少数Oct3 / 4靶基因。在这项研究中，我们发现含F-box的蛋白Fbx15主要在小鼠未分化的ES细胞中表达。 ES细胞中 Oct3 / 4 的失活导致 Fbx15 表达的快速消失。报告基因分析表明，这种ES细胞特异性表达需要一个18 bp的增强子元件，位于转录起始位点上游约500个核苷酸处。该增强剂包含八聚物样基序和相邻的Sox结合基序。任一基序的缺失或点突变消除了增强子活性。当Oct3 / 4和Sox2共表达时，该18 bp片段在NIH 3T3细胞中具有活性。凝胶迁移率变动分析证明Oct3 / 4和Sox2与增强子序列协同结合。在具有敲入 Fbx15 基因座的β-半乳糖苷酶基因的小鼠中，在ES细胞，早期胚胎（两个胚胎，两个胚胎）中检测到5-溴-4-氯-3-吲哚基-β-d-吡喃半乳糖苷染色。细胞到胚泡阶段）和睾丸组织。尽管 Fbx15 有这样的特异性表达，纯合突变小鼠没有明显的发育缺陷，并且能够繁殖。 Fbx15 -null ES细胞的形态，增殖和分化均正常。这些数据表明， Fbx15 是Oct3 / 4的新型靶标，但对于ES细胞的自我更新，发育和繁殖是必不可少的。

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