Identification of an Enhancer That Controls Up-regulation of Fibronectin during Differentiation of Embryonic Stem Cells into Extraembryonic Endoderm*
Identification of an Enhancer That Controls Up-regulation of Fibronectin during Differentiation of Embryonic Stem Cells into Extraembryonic Endoderm*
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DOI：
10.1074/jbc.m410731200
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发表时间：
2005-02
影响因子：
4.8
通讯作者：
Tetsushi Shirai;S. Miyagi;Daisuke Horiuchi;Tomoko Okuda-Katayanagi;M. Nishimoto;M. Muramatsu;Y. Sakamoto;M. Nagata;K. Hagiwara;A. Okuda
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文献类型：
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作者：
Tetsushi Shirai;S. Miyagi;Daisuke Horiuchi;Tomoko Okuda-Katayanagi;M. Nishimoto;M. Muramatsu;Y. Sakamoto;M. Nagata;K. Hagiwara;A. Okuda
胚胎外胚层是小鼠胚胎发生早期胚泡的内细胞群细胞。胚胎外内胚层的形成，后来形成卵黄囊，似乎是内细胞群随后分化的先决条件。虽然胚胎干细胞可以在体外诱导分化为胚胎外内胚层细胞，但这一过程的分子机制尚不清楚。我们使用启动子陷阱方法来寻找在胚胎干细胞中表达并在胚胎外内胚层分化过程中高度上调的基因。我们发现纤维连接蛋白符合这种表达谱。此外，我们在纤维连接蛋白位点的第12个内含子中发现了一个增强子，它再现了纤维连接蛋白的内源性表达模式。该增强子携带Sox蛋白结合序列，我们的分析表明，在胚胎外内胚层中高度表达的Sox7和Sox17参与了增强子的活性。
The extraembryonic endoderm is derived from inner cell mass cells of the blastocyst during early mouse embryogenesis. Formation of the extraembryonic endoderm, which later contributes to the yolk sac, appears to be a prerequisite for subsequent differentiation of the inner cell mass. While embryonic stem cells can be induced to differentiate into extraembryonic endoderm cells in vitro, the molecular mechanisms underlying this process are poorly understood. We used a promoter trap approach to search for genes that are expressed in embryonic stem cells and are highly up-regulated during differentiation to the extraembryonic endoderm fate. We showed that fibronectin fits this expression profile. Moreover we identified an enhancer in the 12th intron of the fibronectin locus that recapitulated the endogenous pattern of fibronectin expression. This enhancer carries Sox protein-binding sequences, and our analysis demonstrated that Sox7 and Sox17, which are highly expressed in the extraembryonic endoderm, were involved in enhancer activity.