Orphan receptor COUP-TF I antagonizes retinoic acid-induced neuronal differentiation.
Chicken ovalbumin upstream promoter-transcription factors (COUP-TF) are expressed in the developing nervous system and interact with nuclear hormone receptors to regulate expression of different genes. The role of COUP-TF orphan receptors in neurogenesis is virtually unknown. To study the possible function of COUP-TF I during neuronal differentiation, we generated COUP-TF I overexpressing teratocarcinoma PCC7 cell lines and analyzed retinoic acid (RA)-induced neuronal differentiation of these cells. COUP-TF I overexpression results in the blockade of morphological differentiation after induction to differentiate. COUP-TF I represses expression of microtubule-associated protein 2 (MAP2) gene and delays induction of growth-associated protein 43 (GAP43) gene expression. In contrast, expression of the neurofilament light subunit (NF-L) gene is not affected by COUP-TF I overexpression during neuronal differentiation. Also, cells overexpressing COUP-TF I do not stop proliferating after RA and dBcAMP treatment and possess suppressed transcriptional activation from different RA response elements. These results suggest that COUP-TF I plays an important role in regulating RA-induced neuronal differentiation.
Neuman
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Department of Anatomy and Neurobiology, Colorado State University, Fort Collins 80523, USA.
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D000818:Animals; D001483:Base Sequence; D015415:Biomarkers; D003994:Bucladesine / Q000494:pharmacology; D051838:COUP Transcription Factor I; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000494:pharmacology*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D019922:GAP-43 Protein; D015870:Gene Expression / Q000502:physiology; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics; D016900:Neurofilament Proteins / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D018243:Teratocarcinoma / Q000473:pathology / Q000503:physiopathology; D014157:Transcription Factors / Q000235:genetics / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000166:cytology
D015415:Biomarkers; D051838:COUP Transcription Factor I; D004268:DNA-Binding Proteins; D019922:GAP-43 Protein; D008562:Membrane Glycoproteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; C497590:Nr2f1 protein, mouse; D011965:Receptors, Glucocorticoid; D014157:Transcription Factors; D014212:Tretinoin; D003994:Bucladesine