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.
Guo
Ying
Y
Department of Medicine and The Walther Oncology Center, R4-202, 1044 West Walnut Street, Indiana University Medical Center, Indianapolis, IN 46202, USA.
Costa
Robert
R
Ramsey
Heather
H
Starnes
Trevor
T
Vance
Gail
G
Robertson
Kent
K
Kelley
Mark
M
Reinbold
Rolland
R
Scholer
Hans
H
Hromas
Robert
R
D001665:Binding Sites; D002460:Cell Line; D019070:Cell Lineage; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004707:Endoderm / Q000166:cytology / Q000378:metabolism*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D051542:Hepatocyte Nuclear Factor 3-beta; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics; D050814:Octamer Transcription Factor-3; D053495:Osteopontin; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013379:Substrate Specificity; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D004268:DNA-Binding Proteins; C496502:FOXA2 protein, human; D009687:Nuclear Proteins; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D012097:Repressor Proteins; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D014157:Transcription Factors; D053495:Osteopontin; D051542:Hepatocyte Nuclear Factor 3-beta; D004247:DNA