GATA factor activity is required for the trophoblast-specific transcriptional regulation of the mouse placental lactogen I gene.
GATA factor activity is required for the trophoblast-specific transcriptional regulation of the mouse placental lactogen I gene.
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发表时间：
1994-11
期刊：
影响因子：
4.6
通讯作者：
Yuk Kiu Ng;Kathleen M. George;J. D. Engel;Daniel I. H. Linzer
中科院分区：
文献类型：
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作者：
Yuk Kiu Ng;Kathleen M. George;J. D. Engel;Daniel I. H. Linzer
控制胎盘中组织特异性基因表达的分子决定因素目前还不清楚，特别是关于特定激素基因的调节，这些激素基因的产物对胚胎发育和维持养育母体的环境至关重要。在继续我们的小鼠胎盘催乳素I基因的滋养层特异性表达的分析中，我们现在证明转录因子加塔-2和加塔-3调节该基因启动子的活性。这些因子在胎盘滋养层细胞中表达，加塔-2、加塔-3和胎盘催乳素I mRNA的峰值水平均在妊娠中期积累。胎盘催乳素I基因启动子的一个区域的分析，以前被证明足以指导滋养层特异性转录，揭示了加塔-2或加塔-3的三个共有结合位点的存在。加塔-2和加塔-3在体外都与这些位点结合，并且这些位点的突变导致启动子活性的显著降低，如通过瞬时转染到表达内源性加塔-2和加塔-3的绒毛膜癌衍生细胞系Rcho-1中所测定的。此外，加塔因子在Rcho-1细胞中的过表达刺激从共转染的胎盘催乳素I基因启动子的转录。最重要的是，发现加塔-2或加塔-3的表达在转染的非滋养层（成纤维细胞）细胞中诱导从该启动子的转录。这些数据表明，加塔因子是胎盘滋养层中限制性和必需的转录调节分子，并且胎盘催乳素I基因的组织特异性至少部分由加塔-2和/或加塔-3决定。
The molecular determinants governing tissue-specific gene expression in the placenta are at present only poorly defined, particularly with respect to the regulation of specific hormone genes whose products are vital to embryonic development and the maintenance of a nurturing maternal environment. In continuing our analysis of the trophoblast-specific expression of the mouse placental lactogen I gene, we now demonstrate that the transcription factors GATA-2 and GATA-3 regulate the activity of this gene promoter. These factors are expressed in placental trophoblast cells, with peak levels of the GATA-2, GATA-3 and placental lactogen I mRNAs each accumulating at midgestation. Analysis of a region of the placental lactogen I gene promoter, previously shown to be sufficient for directing trophoblast-specific transcription, revealed the presence of three consensus binding sites for GATA-2 or GATA-3. Both GATA-2 and GATA-3 bind to these sites in vitro and mutation of these sites results in a significant decrease in promoter activity as assayed by transient transfection into the choriocarcinoma-derived cell line Rcho-1, which expresses endogenous GATA-2 and GATA-3. Furthermore, overexpression of GATA factors in Rcho-1 cells stimulates transcription from a co-transfected placental lactogen I gene promoter. Most significantly, expression of GATA-2 or GATA-3 was found to induce transcription from this promoter in transfected non-trophoblast (fibroblast) cells. These data indicate that GATA factors are both limiting and required transcriptional regulatory molecules in placental trophoblasts, and that the tissue specificity of the placental lactogen I gene is determined, at least in part, by GATA-2 and/or GATA-3.