title: Role of COUP-TFI during retinoic acid-induced differentiation of P19 cells to endodermal cells.
abstract: Retinoic acid (RA) is a positive regulator of P19 cell differentiation. Silencing of pre-B cell leukemia transcription factors (PBXs) expression in P19 cells (AS cells) results in a failure of these cells to differentiate to endodermal cells upon RA treatment. Chicken Ovalbumin Upstream Promoter Transcription Factor I (COUP-TFI) is an orphan member of the steroid-thyroid hormone superfamily. RA treatment of wild type P19 cells results in a dramatic increase in the expression of COUP-TFI; however, COUP-TFI mRNA levels fail to be elevated upon RA treatment of AS cells indicating that PBX expression is required for elevation in COUP-TFI expression. To study the role of COUP-TFI during RA-dependent differentiation of P19 cells, AS cells that inducibly express various levels of COUP-TFI were prepared. Exogenous expression of COUP-TFI in AS cells, in a dose-dependent fashion, leads to growth inhibition, modest cell cycle disruption, and early apoptosis. Furthermore, AS cells can overcome the blockage in RA-dependent differentiation to endodermal cells when either pharmacological levels of COUP-TFI are expressed or a combination of both the expression of physiological levels of COUP-TFI and RA treatment. Additionally, the mRNA level of several pluripotency associated genes including OCT-4, DAX-1, and SF-1 in the COUP-TFI expressing AS cells are reduced. Moreover, analysis of the expression of primary RA response genes indicates that COUP-TFI is involved in the regulatory modulation of the expression of at least two genes, CYP26A1 and HoxA1. These studies demonstrate that COUP-TFI functions as a physiologically relevant regulator during RA-mediated endodermal differentiation of P19 cells.
authors.affiliation: Departments of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Brandy S
authors.initials: BS
authors.lastname: Pickens
authors.forename: Bryan W
authors.initials: BW
authors.lastname: Teets
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Soprano
authors.forename: Dianne Robert
authors.initials: DR
authors.lastname: Soprano
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051838:COUP Transcription Factor I / Q000235:genetics* / Q000378:metabolism; D051837:COUP Transcription Factor II / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics*; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D057137:DAX-1 Orphan Nuclear Receptor / Q000235:genetics / Q000378:metabolism; D004707:Endoderm / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D012333:RNA, Messenger / Q000235:genetics; D000072516:Retinoic Acid 4-Hydroxylase; D054339:Steroidogenic Factor 1 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D000099261:Homeobox A1 Protein
chemical_list: D051838:COUP Transcription Factor I; D051837:COUP Transcription Factor II; D003577:Cytochrome P-450 Enzyme System; D057137:DAX-1 Orphan Nuclear Receptor; D018398:Homeodomain Proteins; D050814:Octamer Transcription Factor-3; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D012333:RNA, Messenger; D000072516:Retinoic Acid 4-Hydroxylase; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; D014212:Tretinoin; D000099261:Homeobox A1 Protein; C539966:Nr0b1 protein, mouse; C497587:Nr2f2 protein, mouse; C481797:Pbx1 protein, mouse; C000607080:Cyp26a1 protein, mouse