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Sophia Y. Tsai - One of the best experts on this subject based on the ideXlab platform.
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elimination of the male reproductive tract in the female embryo is promoted by coup tfII in mice
Yearbook of Paediatric Endocrinology, 2018Co-Authors: Fei Zhao, Mingjer Tsai, Sophia Y. Tsai, Heather L Franco, Karina F Rodriguez, Paula R Brown, Humphrey H C YaoAbstract:The sexual differentiation paradigm contends that the female pattern of the reproductive system is established by default because the male reproductive tracts (Wolffian ducts) in the female degenerate owing to a lack of androgen. Here, we discovered that female mouse embryos lacking Coup-tfII (chicken ovalbumin upstream promoter Transcription Factor II) in the Wolffian duct mesenchyme became intersex—possessing both female and male reproductive tracts. Retention of Wolffian ducts was not caused by ectopic androgen production or action. Instead, enhanced phosphorylated extracellular signal-regulated kinase signaling in Wolffian duct epithelium was responsible for the retention of male structures in an androgen-independent manner. We thus suggest that elimination of Wolffian ducts in female embryos is actively promoted by COUP-TFII, which suppresses a mesenchyme-epithelium cross-talk responsible for Wolffian duct maintenance.
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the role of coup tfII in striated muscle development and disease
Current Topics in Developmental Biology, 2017Co-Authors: Sanpin Wu, Mingjer Tsai, Sophia Y. TsaiAbstract:Skeletal and cardiac muscles are the only striated muscles in the body. Although sharing many structural and functional similarities, skeletal and cardiac muscles have intrinsic differences in terms of physiology and regenerative potential. While skeletal muscle possesses a robust regenerative response, the mammalian heart has limited repair capacity after birth. In this review, we provide an updated view regarding chicken ovalbumin upstream promoter-Transcription Factor II (COUP-TFII) function in vertebrate myogenesis, with particular emphasis on the skeletal and cardiac muscles. We also highlight the new insights of COUP-TFII hyperactivity underlying striated muscle dysfunction. Lastly, we discuss the challenges and strategies in translating COUP-TFII action for clinical intervention.
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endometrial expression of steroidogenic Factor 1 promotes cystic glandular morphogenesis
Molecular Endocrinology, 2016Co-Authors: Yasmin M Vasquez, Matthew L Anderson, Sanpin Wu, Shannon M. Hawkins, Christopher J. Creighton, John P Lydon, Mingjer Tsai, Sophia Y. Tsai, Francesco J DemayoAbstract:Epigenetic silencing of steroidogenic Factor 1 (SF1) is lost in endometriosis, potentially contributing to de novo local steroidogenesis favoring inflammation and growth of ectopic endometrial tissue. In this study, we examine the impact of SF1 expression in the eutopic uterus by a novel mouse model that conditionally expresses SF1 in endometrium. In vivo SF1 expression promoted the development of enlarged endometrial glands and attenuated estrogen and progesterone responsiveness. Endometriosis induction by autotransplantation of uterine tissue to the mesenteric membrane resulted in the increase in size of ectopic lesions from SF1-expressing mice. By integrating the SF1-dependent transcriptome with the whole genome binding profile of SF1, we identified uterine-specific SF1-regulated genes involved in Wingless and Progesterone receptor-Hedgehog-Chicken ovalbumin upstream promoter Transcription Factor II signaling for gland development and epithelium-stroma interaction, respectively. The present results ind...
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Endocardial Cushion Morphogenesis and Coronary Vessel Development Require Chicken Ovalbumin Upstream Promoter-Transcription Factor II
Arteriosclerosis thrombosis and vascular biology, 2012Co-Authors: Fu-jung Lin, Mingjer Tsai, Li-ru You, Wen-hsin Hsu, Sophia Y. TsaiAbstract:Objective— Septal defects and coronary vessel anomalies are common congenital heart defects, yet their ontogeny and the underlying genetic mechanisms are not well understood. Here, we investigated the role of chicken ovalbumin upstream promoter-Transcription Factor II (COUP-TFII, NR2F2) in cardiac organogenesis. Methods and Results— We analyzed embryos deficient in COUP-TFII and observed a spectrum of cardiac defects, including atrioventricular septal defect, thin-walled myocardium, and abnormal coronary morphogenesis. We show by expression analysis that COUP-TFII is expressed in the endocardium and the epicardium but not in the myocardium of the ventricle. Using endothelial-specific COUP-TFII mutants and molecular approaches, we show that COUP-TFII deficiency resulted in endocardial cushion hypoplasia. This was attributed to the reduced growth and survival of atrioventricular cushion mesenchymal cells and defective epithelial-mesenchymal transformation (EMT) in the underlying endocardium. In addition, the endocardial EMT defect was accompanied by downregulation of Snai1 , one of the master regulators of EMT, and upregulation of vascular endothelial-cadherin. Furthermore, we show that although COUP-TFII does not play a major role in the formation of epicardial cell cysts, it is critically important for the formation of epicardium. Ablation of COUP-TFII impairs epicardial EMT and coronary plexus formation. Conclusion— Our results reveal that COUP-TFII plays cell-autonomous roles in the endocardium and the epicardium for endocardial and epicardial EMT, which are required for proper valve and coronary vessel formation during heart development.
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suppression of erα activity by coup tfII is essential for successful implantation and decidualization
Molecular Endocrinology, 2010Co-Authors: Dong Kee Lee, John P Lydon, Francesco J Demayo, Mingjer Tsai, Isao Kurihara, Jae Wook Jeong, Sophia Y. TsaiAbstract:Synchrony between embryo competency and uterine receptivity is essential for successful implantation. Mice with ablation of chicken ovalbumin upstream promoter-Transcription Factor II (COUP-TFII) in the uterus (PR(Cre/+);COUP-TFII(flox/flox)) exhibit implantation defects and increased estrogen receptor (ER)alpha activity in the luminal epithelium, suggesting high ERalpha activity may disrupt the window of uterine receptivity. To determine whether increased ERalpha activity in the PR(Cre/+);COUP-TFII(flox/flox) uterus is the cause of defective implantation, we assessed whether inhibition of ERalpha activity could rescue the PR(Cre/+);COUP-TFII(flox/flox) uterine implantation defect. ICI 182,780 (ICI), a pure ERalpha antagonist, was administered to PR(Cre/+);COUP-TFII(flox/flox) mutant and COUP-TFII(flox/flox) control mice during the receptive period, and the number of implantation sites was examined. COUP-TFII(flox/flox) control mice treated with oil or ICI showed the normal number of implantation sites. As expected, no implantation sites were observed in PR(Cre/+);COUP-TFII(flox/flox) mutant mice treated with oil, consistent with previous observations. In contrast, implantation sites were greatly increased in ICI-treated PR(Cre/+);COUP-TFII(flox/flox) mutant mice, albeit at a reduced number in comparison with the control mice. ICI treatment was also able to restore the expression of Wnt4 and bone morphogenetic protein 2, important for endometrial decidualization in the PR(Cre/+);COUP-TFII(flox/flox) mutant mice. To confirm that the rescue of embryo attachment and decidualization is a consequence of a reduced ERalpha activity upon ICI treatment, we showed a reduction of the expression of ERalpha target genes in PR(Cre/+);COUP-TFII(flox/flox) mutant mice. Because COUP-TFII was also shown in our laboratory to be important for placentation during pregnancy, we asked whether ICI treatment could also rescue the placentation defect to allow full-term pregnancy in these mice. We found that whereas mice were born in COUP-TFII(flox/flox) control mice given ICI, no pups were born in the PR(Cre/+);COUP-TFII(flox/flox) mutant mice, suggesting that the increased ERalpha activity is not the reason for placentation defects. These results demonstrate that during the perIImplantation period, COUP-TFII regulates embryo attachment and decidualization through controlling ERalpha activity. However, COUP-TFII expression is still required in the postimplantation period to facilitate placentation.
Mingjer Tsai - One of the best experts on this subject based on the ideXlab platform.
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elimination of the male reproductive tract in the female embryo is promoted by coup tfII in mice
Yearbook of Paediatric Endocrinology, 2018Co-Authors: Fei Zhao, Mingjer Tsai, Sophia Y. Tsai, Heather L Franco, Karina F Rodriguez, Paula R Brown, Humphrey H C YaoAbstract:The sexual differentiation paradigm contends that the female pattern of the reproductive system is established by default because the male reproductive tracts (Wolffian ducts) in the female degenerate owing to a lack of androgen. Here, we discovered that female mouse embryos lacking Coup-tfII (chicken ovalbumin upstream promoter Transcription Factor II) in the Wolffian duct mesenchyme became intersex—possessing both female and male reproductive tracts. Retention of Wolffian ducts was not caused by ectopic androgen production or action. Instead, enhanced phosphorylated extracellular signal-regulated kinase signaling in Wolffian duct epithelium was responsible for the retention of male structures in an androgen-independent manner. We thus suggest that elimination of Wolffian ducts in female embryos is actively promoted by COUP-TFII, which suppresses a mesenchyme-epithelium cross-talk responsible for Wolffian duct maintenance.
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the role of coup tfII in striated muscle development and disease
Current Topics in Developmental Biology, 2017Co-Authors: Sanpin Wu, Mingjer Tsai, Sophia Y. TsaiAbstract:Skeletal and cardiac muscles are the only striated muscles in the body. Although sharing many structural and functional similarities, skeletal and cardiac muscles have intrinsic differences in terms of physiology and regenerative potential. While skeletal muscle possesses a robust regenerative response, the mammalian heart has limited repair capacity after birth. In this review, we provide an updated view regarding chicken ovalbumin upstream promoter-Transcription Factor II (COUP-TFII) function in vertebrate myogenesis, with particular emphasis on the skeletal and cardiac muscles. We also highlight the new insights of COUP-TFII hyperactivity underlying striated muscle dysfunction. Lastly, we discuss the challenges and strategies in translating COUP-TFII action for clinical intervention.
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endometrial expression of steroidogenic Factor 1 promotes cystic glandular morphogenesis
Molecular Endocrinology, 2016Co-Authors: Yasmin M Vasquez, Matthew L Anderson, Sanpin Wu, Shannon M. Hawkins, Christopher J. Creighton, John P Lydon, Mingjer Tsai, Sophia Y. Tsai, Francesco J DemayoAbstract:Epigenetic silencing of steroidogenic Factor 1 (SF1) is lost in endometriosis, potentially contributing to de novo local steroidogenesis favoring inflammation and growth of ectopic endometrial tissue. In this study, we examine the impact of SF1 expression in the eutopic uterus by a novel mouse model that conditionally expresses SF1 in endometrium. In vivo SF1 expression promoted the development of enlarged endometrial glands and attenuated estrogen and progesterone responsiveness. Endometriosis induction by autotransplantation of uterine tissue to the mesenteric membrane resulted in the increase in size of ectopic lesions from SF1-expressing mice. By integrating the SF1-dependent transcriptome with the whole genome binding profile of SF1, we identified uterine-specific SF1-regulated genes involved in Wingless and Progesterone receptor-Hedgehog-Chicken ovalbumin upstream promoter Transcription Factor II signaling for gland development and epithelium-stroma interaction, respectively. The present results ind...
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Endocardial Cushion Morphogenesis and Coronary Vessel Development Require Chicken Ovalbumin Upstream Promoter-Transcription Factor II
Arteriosclerosis thrombosis and vascular biology, 2012Co-Authors: Fu-jung Lin, Mingjer Tsai, Li-ru You, Wen-hsin Hsu, Sophia Y. TsaiAbstract:Objective— Septal defects and coronary vessel anomalies are common congenital heart defects, yet their ontogeny and the underlying genetic mechanisms are not well understood. Here, we investigated the role of chicken ovalbumin upstream promoter-Transcription Factor II (COUP-TFII, NR2F2) in cardiac organogenesis. Methods and Results— We analyzed embryos deficient in COUP-TFII and observed a spectrum of cardiac defects, including atrioventricular septal defect, thin-walled myocardium, and abnormal coronary morphogenesis. We show by expression analysis that COUP-TFII is expressed in the endocardium and the epicardium but not in the myocardium of the ventricle. Using endothelial-specific COUP-TFII mutants and molecular approaches, we show that COUP-TFII deficiency resulted in endocardial cushion hypoplasia. This was attributed to the reduced growth and survival of atrioventricular cushion mesenchymal cells and defective epithelial-mesenchymal transformation (EMT) in the underlying endocardium. In addition, the endocardial EMT defect was accompanied by downregulation of Snai1 , one of the master regulators of EMT, and upregulation of vascular endothelial-cadherin. Furthermore, we show that although COUP-TFII does not play a major role in the formation of epicardial cell cysts, it is critically important for the formation of epicardium. Ablation of COUP-TFII impairs epicardial EMT and coronary plexus formation. Conclusion— Our results reveal that COUP-TFII plays cell-autonomous roles in the endocardium and the epicardium for endocardial and epicardial EMT, which are required for proper valve and coronary vessel formation during heart development.
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suppression of erα activity by coup tfII is essential for successful implantation and decidualization
Molecular Endocrinology, 2010Co-Authors: Dong Kee Lee, John P Lydon, Francesco J Demayo, Mingjer Tsai, Isao Kurihara, Jae Wook Jeong, Sophia Y. TsaiAbstract:Synchrony between embryo competency and uterine receptivity is essential for successful implantation. Mice with ablation of chicken ovalbumin upstream promoter-Transcription Factor II (COUP-TFII) in the uterus (PR(Cre/+);COUP-TFII(flox/flox)) exhibit implantation defects and increased estrogen receptor (ER)alpha activity in the luminal epithelium, suggesting high ERalpha activity may disrupt the window of uterine receptivity. To determine whether increased ERalpha activity in the PR(Cre/+);COUP-TFII(flox/flox) uterus is the cause of defective implantation, we assessed whether inhibition of ERalpha activity could rescue the PR(Cre/+);COUP-TFII(flox/flox) uterine implantation defect. ICI 182,780 (ICI), a pure ERalpha antagonist, was administered to PR(Cre/+);COUP-TFII(flox/flox) mutant and COUP-TFII(flox/flox) control mice during the receptive period, and the number of implantation sites was examined. COUP-TFII(flox/flox) control mice treated with oil or ICI showed the normal number of implantation sites. As expected, no implantation sites were observed in PR(Cre/+);COUP-TFII(flox/flox) mutant mice treated with oil, consistent with previous observations. In contrast, implantation sites were greatly increased in ICI-treated PR(Cre/+);COUP-TFII(flox/flox) mutant mice, albeit at a reduced number in comparison with the control mice. ICI treatment was also able to restore the expression of Wnt4 and bone morphogenetic protein 2, important for endometrial decidualization in the PR(Cre/+);COUP-TFII(flox/flox) mutant mice. To confirm that the rescue of embryo attachment and decidualization is a consequence of a reduced ERalpha activity upon ICI treatment, we showed a reduction of the expression of ERalpha target genes in PR(Cre/+);COUP-TFII(flox/flox) mutant mice. Because COUP-TFII was also shown in our laboratory to be important for placentation during pregnancy, we asked whether ICI treatment could also rescue the placentation defect to allow full-term pregnancy in these mice. We found that whereas mice were born in COUP-TFII(flox/flox) control mice given ICI, no pups were born in the PR(Cre/+);COUP-TFII(flox/flox) mutant mice, suggesting that the increased ERalpha activity is not the reason for placentation defects. These results demonstrate that during the perIImplantation period, COUP-TFII regulates embryo attachment and decidualization through controlling ERalpha activity. However, COUP-TFII expression is still required in the postimplantation period to facilitate placentation.
Martin Klingenspor - One of the best experts on this subject based on the ideXlab platform.
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chicken ovalbumin upstream promoter Transcription Factor II regulates uncoupling protein 3 gene Transcription in phodopus sungorus
BMC Molecular Biology, 2007Co-Authors: Tobias Fromme, Kathrin Reichwald, Matthias Platzer, Martin KlingensporAbstract:Background Ucp3 is an integral protein of the inner mitochondrial membrane with a role in lipid metabolism preventing deleterious effects of fatty acids in states of high lipid oxidation. Ucp3 is expressed in brown adipose tissue and skeletal muscle and controlled by a Transcription Factor complex including PPARalpha, MyoD and the histone acetyltransferase p300. Several studies have demonstrated interaction of these Factors with chicken ovalbumin upstream promoter Transcription Factor II (Coup-TFII). This nuclear receptor is involved in organogenesis and other developmental processes including skeletal muscle development, but also co-regulates a number of metabolic genes. In this study we in silico analyzed the upstream region of Ucp3 of the Djungarian hamster Phodopus sungorus and identified several putative response elements for Coup-TFII. We therefore investigated whether Coup-TFII is a further player in the Transcriptional control of the Ucp3 gene in rodents.
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chicken ovalbumin upstream promoter Transcription Factor II regulates uncoupling protein 3 gene Transcription in phodopus sungorus
BMC Molecular Biology, 2007Co-Authors: Tobias Fromme, Kathrin Reichwald, Matthias Platzer, Martin KlingensporAbstract:Ucp3 is an integral protein of the inner mitochondrial membrane with a role in lipid metabolism preventing deleterious effects of fatty acids in states of high lipid oxidation. Ucp3 is expressed in brown adipose tissue and skeletal muscle and controlled by a Transcription Factor complex including PPARalpha, MyoD and the histone acetyltransferase p300. Several studies have demonstrated interaction of these Factors with chicken ovalbumin upstream promoter Transcription Factor II (Coup-TFII). This nuclear receptor is involved in organogenesis and other developmental processes including skeletal muscle development, but also co-regulates a number of metabolic genes. In this study we in silico analyzed the upstream region of Ucp3 of the Djungarian hamster Phodopus sungorus and identified several putative response elements for Coup-TFII. We therefore investigated whether Coup-TFII is a further player in the Transcriptional control of the Ucp3 gene in rodents. By quantitative PCR we demonstrated a positive correlation of Coup-TFII and Ucp3 mRNA expression in skeletal muscle and brown adipose tissue in response to food deprivation and cold exposure, respectively. In reporter gene assays Coup-TFII enhanced transactivation of the Ucp3 promoter conveyed by MyoD, PPARalpha, RXRalpha and/or p300. Using deletions and mutated constructs, we identified a Coup-TFII enhancer element 816–840 bp upstream of the Transcriptional start site. Binding of Coup-TFII to this upstream enhancer was confirmed in electrophoretic mobility shift and supershift assays. Transcriptional regulation of the Coup-TFII gene in response to starvation and cold exposure seems to be the regulatory mechanism of Ucp3 mRNA expression in brown adipose and skeletal muscle tissue determining the final appropriate rate of transcript synthesis. These findings add a crucial component to the complex Transcriptional machinery controlling expression of Ucp3. Given the substantial evidence for a function of Ucp3 in lipid metabolism, Coup-TFII may not only be a negative regulator of glucose responsive genes but also transactivate genes involved in lipid metabolism.
Evan D Rosen - One of the best experts on this subject based on the ideXlab platform.
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the orphan nuclear receptor chicken ovalbumin upstream promoter Transcription Factor II is a critical regulator of adipogenesis
Proceedings of the National Academy of Sciences of the United States of America, 2008Co-Authors: Chung Hsin Hsu, Jun Eguchi, Evan D RosenAbstract:The orphan nuclear receptor chicken ovalbumin upstream promoter-Transcription Factor II (COUP-TFII; Nr2f2) is expressed in adipose tissue in vivo and declines during differentiation. Overexpression of COUP-TFII prevents adipogenesis, whereas shRNA-mediated reduction of COUP-TFII promotes differentiation, as shown by increased lipid accumulation and elevated expression of fat cell marker proteins. Furthermore, reduction of COUP-TFII allows uncommitted fibroblasts to be differentiated into fat cells. COUP-TFII represses the expression of a number of proadipogenic Factors in adipocytes, with direct action noted at the CAAT enhancer-binding protein α promoter. We show that COUP-TFII acts downstream of hedgehog signaling and is required for the full antiadipogenic effect of this pathway. This effect is mediated in part by interaction with GATA Factors. COUP-TFII and GATA2 are physically associated and repress target gene expression in an additive manner. Taken together, our data demonstrate that COUP-TFII represents an endogenous suppressor of adipogenesis, linking antiadipogenic extracellular signals to the core Transcriptional cascade.
Tobias Fromme - One of the best experts on this subject based on the ideXlab platform.
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chicken ovalbumin upstream promoter Transcription Factor II regulates uncoupling protein 3 gene Transcription in phodopus sungorus
BMC Molecular Biology, 2007Co-Authors: Tobias Fromme, Kathrin Reichwald, Matthias Platzer, Martin KlingensporAbstract:Background Ucp3 is an integral protein of the inner mitochondrial membrane with a role in lipid metabolism preventing deleterious effects of fatty acids in states of high lipid oxidation. Ucp3 is expressed in brown adipose tissue and skeletal muscle and controlled by a Transcription Factor complex including PPARalpha, MyoD and the histone acetyltransferase p300. Several studies have demonstrated interaction of these Factors with chicken ovalbumin upstream promoter Transcription Factor II (Coup-TFII). This nuclear receptor is involved in organogenesis and other developmental processes including skeletal muscle development, but also co-regulates a number of metabolic genes. In this study we in silico analyzed the upstream region of Ucp3 of the Djungarian hamster Phodopus sungorus and identified several putative response elements for Coup-TFII. We therefore investigated whether Coup-TFII is a further player in the Transcriptional control of the Ucp3 gene in rodents.
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chicken ovalbumin upstream promoter Transcription Factor II regulates uncoupling protein 3 gene Transcription in phodopus sungorus
BMC Molecular Biology, 2007Co-Authors: Tobias Fromme, Kathrin Reichwald, Matthias Platzer, Martin KlingensporAbstract:Ucp3 is an integral protein of the inner mitochondrial membrane with a role in lipid metabolism preventing deleterious effects of fatty acids in states of high lipid oxidation. Ucp3 is expressed in brown adipose tissue and skeletal muscle and controlled by a Transcription Factor complex including PPARalpha, MyoD and the histone acetyltransferase p300. Several studies have demonstrated interaction of these Factors with chicken ovalbumin upstream promoter Transcription Factor II (Coup-TFII). This nuclear receptor is involved in organogenesis and other developmental processes including skeletal muscle development, but also co-regulates a number of metabolic genes. In this study we in silico analyzed the upstream region of Ucp3 of the Djungarian hamster Phodopus sungorus and identified several putative response elements for Coup-TFII. We therefore investigated whether Coup-TFII is a further player in the Transcriptional control of the Ucp3 gene in rodents. By quantitative PCR we demonstrated a positive correlation of Coup-TFII and Ucp3 mRNA expression in skeletal muscle and brown adipose tissue in response to food deprivation and cold exposure, respectively. In reporter gene assays Coup-TFII enhanced transactivation of the Ucp3 promoter conveyed by MyoD, PPARalpha, RXRalpha and/or p300. Using deletions and mutated constructs, we identified a Coup-TFII enhancer element 816–840 bp upstream of the Transcriptional start site. Binding of Coup-TFII to this upstream enhancer was confirmed in electrophoretic mobility shift and supershift assays. Transcriptional regulation of the Coup-TFII gene in response to starvation and cold exposure seems to be the regulatory mechanism of Ucp3 mRNA expression in brown adipose and skeletal muscle tissue determining the final appropriate rate of transcript synthesis. These findings add a crucial component to the complex Transcriptional machinery controlling expression of Ucp3. Given the substantial evidence for a function of Ucp3 in lipid metabolism, Coup-TFII may not only be a negative regulator of glucose responsive genes but also transactivate genes involved in lipid metabolism.