Abstract
The POU-domain transcription factor Oct4 is essential for the maintenance of the mammalian germline. In this study, we show that the germ cell nuclear factor (GCNF), an orphan nuclear receptor, represses Oct4 gene activity by specifically binding within the proximal promoter. GCNF expression inversely correlates with Oct4 expression in differentiating embryonal cells. GCNF overexpression in embryonal cells represses Oct4 gene and transgene activities, and we establish a link to transcriptional corepressors mediating repression by GCNF. In GCNF-deficient mouse embryos, Oct4 expression is no longer restricted to the germ cell lineage after gastrulation. Our studies suggest that GCNF is critical in repressing Oct4 gene activity as pluripotent stem cells differentiate and in confining Oct4 expression to the germline.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antineoplastic Agents / pharmacology
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Cell Differentiation / physiology
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Cell Line
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Cell Lineage
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Embryo, Mammalian / cytology
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Embryo, Mammalian / drug effects
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Embryo, Mammalian / physiology*
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Fushi Tarazu Transcription Factors
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Gene Expression Regulation
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Gene Expression Regulation, Developmental / physiology
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Genes, Reporter
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Germ Cells / physiology*
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Homeodomain Proteins
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In Situ Hybridization
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Macromolecular Substances
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Mice
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Mice, Knockout
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Nuclear Proteins / metabolism
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Nuclear Receptor Co-Repressor 1
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Nuclear Receptor Subfamily 6, Group A, Member 1
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Octamer Transcription Factor-3
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Promoter Regions, Genetic / genetics
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / metabolism*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Repressor Proteins / metabolism
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Steroidogenic Factor 1
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transgenes / genetics
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Tretinoin / pharmacology
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Two-Hybrid System Techniques
Substances
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Antineoplastic Agents
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DNA-Binding Proteins
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Fushi Tarazu Transcription Factors
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Homeodomain Proteins
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Macromolecular Substances
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Ncor1 protein, mouse
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Nr6a1 protein, mouse
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Nuclear Proteins
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Nuclear Receptor Co-Repressor 1
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Nuclear Receptor Subfamily 6, Group A, Member 1
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Octamer Transcription Factor-3
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Pou5f1 protein, mouse
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Receptors, Cytoplasmic and Nuclear
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Recombinant Fusion Proteins
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Repressor Proteins
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Steroidogenic Factor 1
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Transcription Factors
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Tretinoin