The embryonic stem cell transcription factors Oct-4 and FoxD3 interact to regulate endodermal-specific promoter expression.

The POU homeodomain protein Oct-4 and the Forkhead Box protein FoxD3 (previously Genesis) are transcriptional regulators expressed in embryonic stem cells. Down-regulation of Oct-4 during gastrulation is essential for proper endoderm development. After gastrulation, FoxD3 is generally down-regulated during early endoderm formation, although it specifically remains expressed in the embryonic ...
neural crest. In these studies, we have found that Oct-4 and FoxD3 can bind to identical regulatory DNA sequences. In addition, Oct-4 physically interacted with the FoxD3 DNA-binding domain. Cotransfection of Oct-4 and FoxD3 expression vectors activated the osteopontin enhancer, which is expressed in totipotent embryonic stem cells. FoxA1 and FoxA2 (previously HNF-3alpha and HNF-3beta) are Forkhead Box transcription factors that participate in liver and lung formation from foregut endoderm. Although FoxD3 activated the FoxA1 and FoxA2 promoters, Oct-4 inhibited FoxD3 activation of the FoxA1 and FoxA2 endodermal promoters. These data indicate that Oct-4 functions as a corepressor of FoxD3 to provide embryonic lineage-specific transcriptional regulatory activity to maintain appropriate developmental timing.
Mesh Terms:
Binding Sites, Cell Line, Cell Lineage, DNA, DNA-Binding Proteins, Endoderm, Enhancer Elements, Genetic, Gene Expression Regulation, Developmental, Hepatocyte Nuclear Factor 3-beta, Humans, Nuclear Proteins, Octamer Transcription Factor-3, Osteopontin, Promoter Regions, Genetic, Protein Binding, Protein Structure, Tertiary, Repressor Proteins, Sialoglycoproteins, Stem Cells, Substrate Specificity, Transcription Factors, Transfection
Proc. Natl. Acad. Sci. U.S.A.
Date: Mar. 19, 2002
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