Format

Send to

Choose Destination
See comment in PubMed Commons below
Birth Defects Res A Clin Mol Teratol. 2009 Apr;85(4):303-13. doi: 10.1002/bdra.20537.

Regulation of folate receptor 1 gene expression in the visceral endoderm.

Author information

1
Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana, USA. michael.salbaum@pbrc.edu

Abstract

BACKGROUND:

Nutrient 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 of FOLR1 in the visceral endoderm are unknown.

METHODS:

Sequences 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.

RESULTS:

With F9 embryo carcinoma cells as a model for extraembryonic endoderm, we demonstrate that the P4 promoter of the human FOLR1 gene 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 human FOLR1 gene 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.

CONCLUSIONS:

We have identified a transcriptional enhancer sequence from the FOLR1 locus with specific activity in vitro and in vivo, and suggest that FOLR1 is a target for regulation by HNF4-alpha.

PMID:
19180647
PMCID:
PMC2731486
DOI:
10.1002/bdra.20537
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley Icon for PubMed Central
    Loading ...
    Support Center