Regulation of the Oct-4 gene by nuclear receptors.
To unravel the network of transcription factors established during development it is important to understand how genes specifically expressed during embryogenesis are regulated. Oct-4 is a transcription factor whose expression is associated with an undifferentiated cell phenotype in the early mouse embryo and is downregulated when such cells differentiate. An enhancer in the upstream region of Oct-4 has previously been reported as being sufficient to mediate the cell-type specific expression and RA-dependent down-regulation in EC cells, although the enhancer contains no retinoic acid receptor (RAR) binding sites. Here we report the identification of promoter elements important for the regulation of the Oct-4 gene in EC cells. A region of the proximal Oct-4 promoter contains an overlapping set of regulatory elements including a high affinity binding site for Sp1 and three direct repeats of an AGGTCA-like sequence with either +1 or 0 spacing. Binding and transient transfection assays reveal that Oct-4 is subject to negative regulation by different members of the steroid-thyroid hormone receptor superfamily. Specifically, important roles for ARP-1 and RAR in Oct-4 expression are indicated.
Sylvester
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EMBL, Gene Expression Programme, Heidelberg, Germany.
Schöler
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HR
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D051837:COUP Transcription Factor II; D051836:COUP Transcription Factors; D002467:Cell Nucleus; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D054278:Embryonal Carcinoma Stem Cells; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008969:Molecular Sequence Data; D014411:Neoplastic Stem Cells; D050814:Octamer Transcription Factor-3; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D011987:Receptors, Steroid / Q000502:physiology*; D011988:Receptors, Thyroid Hormone / Q000502:physiology*; D012045:Regulatory Sequences, Nucleic Acid; D012091:Repetitive Sequences, Nucleic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000235:genetics*; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D051837:COUP Transcription Factor II; D051836:COUP Transcription Factors; D004268:DNA-Binding Proteins; C497587:Nr2f2 protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014212:Tretinoin