Weber H, Strandmann E P, Holewa B, Bartkowski S, Zapp D, Zoidl C, Ryffel G U
Institut für Zellbiologie (Tumorforschung), Universitätsklinikum, Essen, Germany.
Int J Dev Biol. 1996 Feb;40(1):297-304.
We review the data available on the structure, developmental appearance and embryonic regulation of the tissue-specific transcription factor HNF1 alpha (LFB1) in Xenopus. The expression of the HNF1 alpha gene starts early in embryogenesis shortly after mid-blastula transition and the protein accumulates in the region of the embryo where liver, pronephros and gut--tissues that contain HNF1 alpha in the adult--are developing. The cofactor DCoH, known to stabilize dimer formation of HNF1 alpha, is present as a maternal factor in the egg and has a partially distinct tissue distribution compared to HNF1 alpha. This implies that DCoH does not only modulate HNF1 alpha dimerization but may also cooperate with other transcription factors. By injecting HNF1 alpha promoter CAT constructs into fertilized Xenopus eggs we obtained activation of the injected gene restricted to the region of the developing larvae expressing endogenous HNF1 alpha. Deletion analysis allowed to define the OZ-element that is essential for embryonic activation. This element also occurs in other promoters activated at mid-blastula transition in the embryo and interacts with the maternal factor OZ-1. As the HNF1 alpha promoter also contains functional binding sites for HNF4 and HNF1, we postulate that all of these transcription factors contribute to the cascade leading to proper embryonic activation of the HNF1 alpha gene.
我们回顾了非洲爪蟾中组织特异性转录因子HNF1α（LFB1）的结构、发育外观及胚胎调控方面的现有数据。HNF1α基因在胚胎发育早期、囊胚中期转换后不久开始表达，其蛋白质在胚胎中肝脏、前肾和肠道（成体中含有HNF1α的组织）发育的区域积累。已知能稳定HNF1α二聚体形成的辅因子DCoH，在卵中作为母体因子存在，与HNF1α相比，其组织分布部分不同。这意味着DCoH不仅调节HNF1α二聚化，还可能与其他转录因子协同作用。通过将HNF1α启动子CAT构建体注射到非洲爪蟾受精卵中，我们发现注射基因的激活仅限于发育中的幼虫中表达内源性HNF1α的区域。缺失分析确定了对胚胎激活至关重要的OZ元件。该元件也存在于胚胎囊胚中期转换时被激活的其他启动子中，并与母体因子OZ-1相互作用。由于HNF1α启动子还含有HNF4和HNF1的功能性结合位点，我们推测所有这些转录因子都参与了导致HNF1α基因正确胚胎激活的级联反应。
