Bossard P, Zaret K S
Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912, USA.
Development. 1998 Dec;125(24):4909-17. doi: 10.1242/dev.125.24.4909.
Gene inactivation studies have shown that members of the GATA family of transcription factors are critical for endoderm differentiation in mice, flies and worms, yet how these proteins function in such a conserved developmental context has not been understood. We use in vivo footprinting of mouse embryonic endoderm cells to show that a DNA-binding site for GATA factors is occupied on a liver-specific, transcriptional enhancer of the serum albumin gene. GATA site occupancy occurs in gut endoderm cells at their pluripotent stage: the cells have the potential to initiate tissue development but they have not yet been committed to express albumin or other tissue-specific genes. The GATA-4 isoform accounts for about half of the nuclear GATA-factor-binding activity in the endoderm. GATA site occupancy persists during hepatic development and is necessary for the activity of albumin gene enhancer. Thus, GATA factors in the endoderm are among the first to bind essential regulatory sites in chromatin. Binding occurs prior to activation of gene expression, changes in cell morphology or functional commitment that would indicate differentiation. We suggest that GATA factors at target sites in chromatin may generally help potentiate gene expression and tissue specification in metazoan endoderm development.
基因失活研究表明，转录因子GATA家族成员对于小鼠、果蝇和线虫的内胚层分化至关重要，但这些蛋白质在如此保守的发育背景下如何发挥作用尚不清楚。我们利用小鼠胚胎内胚层细胞的体内足迹法表明，血清白蛋白基因肝脏特异性转录增强子上存在一个GATA因子的DNA结合位点。GATA位点占据发生在肠道内胚层细胞的多能阶段：这些细胞有启动组织发育的潜力，但尚未开始表达白蛋白或其他组织特异性基因。GATA-4异构体约占内胚层核GATA因子结合活性的一半。GATA位点占据在肝脏发育过程中持续存在，并且对于白蛋白基因增强子的活性是必需的。因此，内胚层中的GATA因子是最早结合染色质中必需调控位点的因子之一。结合发生在基因表达激活、细胞形态变化或表明分化的功能特化之前。我们认为，染色质中靶位点的GATA因子通常可能有助于后生动物内胚层发育中的基因表达增强和组织特化。
