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

Ying Guo, Robert Costa, Heather Ramsey, Trevor Starnes, Gail Vance, Kent Robertson, Mark Kelley, Rolland Reinbold, Hans Scholer, Robert A Hromas

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

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-3α and HNF-3β) 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.

Original languageEnglish (US)
Pages (from-to)3663-3667
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number6
DOIs
StatePublished - Mar 19 2002
Externally publishedYes

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Octamer Transcription Factor-3
Endoderm
Stem Cell Factor
Embryonic Stem Cells
Forkhead Transcription Factors
Gastrulation
Totipotent Stem Cells
POU Domain Factors
Homeodomain Proteins
Co-Repressor Proteins
Osteopontin
Neural Crest
Down-Regulation
Lung
Liver
DNA

ASJC Scopus subject areas

  • General

Cite this

The embryonic stem cell transcription factors Oct-4 and FoxD3 interact to regulate endodermal-specific promoter expression. / Guo, Ying; Costa, Robert; Ramsey, Heather; Starnes, Trevor; Vance, Gail; Robertson, Kent; Kelley, Mark; Reinbold, Rolland; Scholer, Hans; Hromas, Robert A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 6, 19.03.2002, p. 3663-3667.

Research output: Contribution to journalArticle

Guo, Ying ; Costa, Robert ; Ramsey, Heather ; Starnes, Trevor ; Vance, Gail ; Robertson, Kent ; Kelley, Mark ; Reinbold, Rolland ; Scholer, Hans ; Hromas, Robert A. / The embryonic stem cell transcription factors Oct-4 and FoxD3 interact to regulate endodermal-specific promoter expression. In: Proceedings of the National Academy of Sciences of the United States of America. 2002 ; Vol. 99, No. 6. pp. 3663-3667.
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