Open AccessThe embryonic stem cell transcription factors Oct-4 and FoxD3 interact to regulate endodermal-specific promoter expression
Author(s) -
Ying Guo,
Robert H. Costa,
H. E. Ramsey,
Trevor Starnes,
Gail H. Vance,
Kent A. Robertson,
Mark R. Kelley,
Rolland Reinbold,
Hans R. Schöler,
Robert Hromas
Publication year - 2002
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.062041099
Subject(s) - foxa2 , endoderm , biology , foxa1 , transcription factor , pou domain , forkhead transcription factors , enhancer , microbiology and biotechnology , embryonic stem cell , gastrulation , promoter , homeobox , genetics , gene expression , gene
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.