Regulation of folate receptor 1 gene expression in the visceral endoderm.
Regulation of folate receptor 1 gene expression in the visceral endoderm.
复制标题
内脏内胚层叶酸受体 1 基因表达的调节。
DOI：
10.1002/bdra.20537
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Kappen,Claudia
中科院分区：
文献类型：
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作者：
Salbaum,JMichael;Finnell,RichardH;Kappen,Claudia
BACKGROUNDNutrient supply to the developing mammalian embryo is a fundamental requirement. Before completion of the chorioallantoic placenta, the visceral endoderm plays a crucial role in nurturing the embryo. We have found that visceral endoderm cells express folate receptor 1, a high‐affinity receptor for the essential micronutrient folic acid, suggesting that the visceral endoderm has an important function for folate transport to the embryo. The mechanisms that direct expression ofFOLR1in the visceral endoderm are unknown.METHODSSequences were tested for transcriptional activation capabilities in the visceral endoderm utilizing reporter gene assays in a cell model for extraembryonic endoderm in vitro, and in transgenic mice in vivo.RESULTSWith F9 embryo carcinoma cells as a model for extraembryonic endoderm, we demonstrate that the P4 promoter of the humanFOLR1gene is active during differentiation of the cells towards visceral endoderm. However, transgenic mouse experiments show that promoter sequences alone are insufficient to elicit reporter gene transcription in vivo. Using sequence conservation as guide to choose genomic sequences from the humanFOLR1gene locus, we demonstrate that the sequence termed F1CE2 exhibits specific enhancer activity in F9 cells in vitro, in the visceral endoderm, and later the yolk sac in transgenic mouse embryos in vivo. We further show that the transcription factor HNF4‐alpha can activate this enhancer sequence.CONCLUSIONSWe have identified a transcriptional enhancer sequence from theFOLR1locus with specific activity in vitro and in vivo, and suggest thatFOLR1is a target for regulation by HNF4‐alpha. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc.
