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: Brandy S Pickens, Bryan W Teets, Kenneth J Soprano, Dianne Robert Soprano
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 228 Issue 4 Pg. 791-800 (Apr 2013) ISSN: 1097-4652 [Electronic] United States
• PMID: 23018522 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2012 Wiley Periodicals, Inc.

Chemical References

• COUP Transcription Factor I
• COUP Transcription Factor II
• DAX-1 Orphan Nuclear Receptor
• Homeodomain Proteins
• Nr0b1 protein, mouse
• Nr2f2 protein, mouse
• Octamer Transcription Factor-3
• Pbx1 protein, mouse
• Pre-B-Cell Leukemia Transcription Factor 1
• RNA, Messenger
• Steroidogenic Factor 1
• Transcription Factors
• homeobox A1 protein
• Tretinoin
• Cytochrome P-450 Enzyme System
• Cyp26a1 protein, mouse
• Retinoic Acid 4-Hydroxylase

Topics

• Animals
• Apoptosis (drug effects, genetics)
• COUP Transcription Factor I (genetics, metabolism)
• COUP Transcription Factor II (genetics, metabolism)
• Cell Cycle (drug effects, genetics)
• Cell Differentiation (drug effects, genetics)
• Cells, Cultured
• Cytochrome P-450 Enzyme System (genetics, metabolism)
• DAX-1 Orphan Nuclear Receptor (genetics, metabolism)
• Endoderm (cytology, drug effects, metabolism)
• Gene Expression (drug effects, genetics)
• Homeodomain Proteins (genetics, metabolism)
• Mice
• Octamer Transcription Factor-3 (genetics, metabolism)
• Pre-B-Cell Leukemia Transcription Factor 1
• RNA, Messenger (genetics)
• Retinoic Acid 4-Hydroxylase
• Steroidogenic Factor 1 (genetics, metabolism)
• Transcription Factors (genetics, metabolism)
• Tretinoin (pharmacology)