LEF1/TCFs are high mobility group box-containing transcriptional factors mediating canonical Wnt/β-catenin signaling during early embryogenesis and tumorigenesis. β-Catenin forms a complex with LEF 1/TCFs and transa...LEF1/TCFs are high mobility group box-containing transcriptional factors mediating canonical Wnt/β-catenin signaling during early embryogenesis and tumorigenesis. β-Catenin forms a complex with LEF 1/TCFs and transactivates LEF1/TCF-mediated transcriptions during dorsalization. Although LEF-mediated transcription is also implicated in ventralization, the underlying molecular mechanism is not well understood. Using the vertebrate Xenopus laevis model system, we found that Xom, which is a ventralizing homeobox protein with dual roles of transcriptional activation and repression, forms a complex with LEF 1/TCF through its homeodomain and transactivates LEF 1/TCF-mediated transcription through its N-terminal transactivation domain （TAD）. Our data show that Xom lacking the N-terminal TAD fails to transactivate ventral genes, such as BMP4 and Xom itself, but retains the ability to suppress transcriptional activation of dorsal gene promoters, such as the Goosecoid promoter, indicating that transactivation and repression are separable functions of Xom. It has been postulated that Xom forms a positive re-enforcement loop with BMP4 to promote ventral- ization and to suppress dorsal gene expression. Consistent with an essential role of Xom transactivation of LEF1/TCFs during early embryogenesis, we found that expression of the dominant-negative Xom mutant that lacks the TAD fails to re-enforce the ventral signaling of BMP4 and causes a catastrophic effect during gastrulation. Our data suggest that the functional interaction of Xom and LEF 1/TCF-factors is essential for ventral cell fate determination and that LEF 1/TCF factors may function as a point of convergence to mediate the combined signaling of Wnt/β-catenin and BMP4/Xom pathways during early embryogenesis.展开更多
Kruppel-like factor 4（Klf4） is a zinc finger transcription factor and plays crucial roles in Xenopus embryogenesis.However, its regulation during embryogenesis is still unclear. Here, we report that Tcf711, a key do...Kruppel-like factor 4（Klf4） is a zinc finger transcription factor and plays crucial roles in Xenopus embryogenesis.However, its regulation during embryogenesis is still unclear. Here, we report that Tcf711, a key downstream transducer of the Wnt signaling pathway, could promote Klf4 transcription and stimulate Klf4 promoter activity in early Xenopus embryos. Furthermore, cycloheximide treatment showed a direct effect on Klf4 transcription facilitated by Tcf711. Moreover, the dominant negative form of Tcf711（dnTcf711）, which lacks N-terminus of the β-catenin binding motif, could still activate Klf4 transcription, suggesting that this regulation is Wnt/β-catenin independent.Taken together, our results demonstrate that Tcf711 lies upstream of Klf4 to maintain its expression level during Xenopus embryogenesis.展开更多
Both the Wnt/β-catenin and Bone morphogenetic protein （Bmp） signaling pathways play critical roles in dorsal-ventral patterning of the Xenopus embryos. The lymphoid enhancer binding factor （Lef） / T cell factor ...Both the Wnt/β-catenin and Bone morphogenetic protein （Bmp） signaling pathways play critical roles in dorsal-ventral patterning of the Xenopus embryos. The lymphoid enhancer binding factor （Lef） / T cell factor （Tcf） have been viewed as dedicated transcription factors of the Wnt/β-catenin signaling pathway that are activated by β-catenin binding. Now a Xenopus ventral specific transcription factor Xom has also been identified to bear transactivation activity by binding to Lef/Tcf factors [1].展开更多
the left-behind children is appeared in our city in the process, there are many factors that influence the well-being, in this paper I conducted about the influence of left-behind children happiness questionnaire, foc...the left-behind children is appeared in our city in the process, there are many factors that influence the well-being, in this paper I conducted about the influence of left-behind children happiness questionnaire, focuses on the analysis of the influence factors from three aspects of environmental factors, personality factors and social factors. Based on the analys：is results, put forward and strengthen left-behind chi]dren well-being measures.展开更多
Skeletal muscles are essential for locomotion,posture,and metabolic regulation.To understand physiological processes,exercise adaptation,and muscle-related disorders,it is critical to understand the molecular pathways...Skeletal muscles are essential for locomotion,posture,and metabolic regulation.To understand physiological processes,exercise adaptation,and muscle-related disorders,it is critical to understand the molecular pathways that underlie skeletal muscle function.The process of muscle contra ction,orchestrated by a complex interplay of molecular events,is at the core of skeletal muscle function.Muscle contraction is initiated by an action potential and neuromuscular transmission requiring a neuromuscular junction.Within muscle fibers,calcium ions play a critical role in mediating the interaction between actin and myosin filaments that generate force.Regulation of calcium release from the sarcoplasmic reticulum plays a key role in excitation-contraction coupling.The development and growth of skeletal muscle are regulated by a network of molecular pathways collectively known as myogenesis.Myogenic regulators coordinate the diffe rentiation of myoblasts into mature muscle fibers.Signaling pathways regulate muscle protein synthesis and hypertrophy in response to mechanical stimuli and nutrient availability.Seve ral muscle-related diseases,including congenital myasthenic disorders,sarcopenia,muscular dystrophies,and metabolic myopathies,are underpinned by dys regulated molecular pathways in skeletal muscle.Therapeutic interventions aimed at preserving muscle mass and function,enhancing regeneration,and improving metabolic health hold promise by targeting specific molecular pathways.Other molecular signaling pathways in skeletal muscle include the canonical Wnt signaling pathway,a critical regulator of myogenesis,muscle regeneration,and metabolic function,and the Hippo signaling pathway.In recent years,more details have been uncovered about the role of these two pathways during myogenesis and in developing and adult skeletal muscle fibers,and at the neuromuscular junction.In fact,research in the last few years now suggests that these two signaling pathways are interconnected and that they jointly control physiological and pathophysiological processes in muscle fibers.In this review,we will summarize and discuss the data on these two pathways,focusing on their concerted action next to their contribution to skeletal muscle biology.However,an in-depth discussion of the noncanonical Wnt pathway,the fibro/a dipogenic precursors,or the mechanosensory aspects of these pathways is not the focus of this review.展开更多
[Objectives]This study was conducted to investigate characteristics of the human TCF7 L2 gene promoter.[Methods]The 2000 bp sequence of the 5’regulatory region of the human TCF7 L2 gene was obtained from the UCSC gen...[Objectives]This study was conducted to investigate characteristics of the human TCF7 L2 gene promoter.[Methods]The 2000 bp sequence of the 5’regulatory region of the human TCF7 L2 gene was obtained from the UCSC genome database.The promoter,transcription factor binding sites,CpG islands,SNPs and so on were analyzed by a variety of online softwares.[Results]The bioinformatics analysis results showed there were at least 5 potential promoters in the positive-sense strand of the 2000 bp sequence,among which-242--192 bp,-853--803 bp might contain core promoters.A TATA box and a CpG island with a length of 499 bp were found.241,944 and 1035(positive-sense strand)transcription factor binding sites were predicted by the AliBaba2.1,PROMO and JASPAR softwares,respectively.207 common transcription factor binding sites in the conserved region of human and mouse homologous TCF7 L2 gene promoter were identified with CONREAL program,involving 66 kinds of transcription factors.Two SNPs were found in the promoter region.[Conclusions]The promoter of the human TCF7 L2 gene was analyzed by bioinformatics,and the promoter characteristics were obtained.展开更多
文摘LEF1/TCFs are high mobility group box-containing transcriptional factors mediating canonical Wnt/β-catenin signaling during early embryogenesis and tumorigenesis. β-Catenin forms a complex with LEF 1/TCFs and transactivates LEF1/TCF-mediated transcriptions during dorsalization. Although LEF-mediated transcription is also implicated in ventralization, the underlying molecular mechanism is not well understood. Using the vertebrate Xenopus laevis model system, we found that Xom, which is a ventralizing homeobox protein with dual roles of transcriptional activation and repression, forms a complex with LEF 1/TCF through its homeodomain and transactivates LEF 1/TCF-mediated transcription through its N-terminal transactivation domain （TAD）. Our data show that Xom lacking the N-terminal TAD fails to transactivate ventral genes, such as BMP4 and Xom itself, but retains the ability to suppress transcriptional activation of dorsal gene promoters, such as the Goosecoid promoter, indicating that transactivation and repression are separable functions of Xom. It has been postulated that Xom forms a positive re-enforcement loop with BMP4 to promote ventral- ization and to suppress dorsal gene expression. Consistent with an essential role of Xom transactivation of LEF1/TCFs during early embryogenesis, we found that expression of the dominant-negative Xom mutant that lacks the TAD fails to re-enforce the ventral signaling of BMP4 and causes a catastrophic effect during gastrulation. Our data suggest that the functional interaction of Xom and LEF 1/TCF-factors is essential for ventral cell fate determination and that LEF 1/TCF factors may function as a point of convergence to mediate the combined signaling of Wnt/β-catenin and BMP4/Xom pathways during early embryogenesis.
基金supported by the Start-up Funding of Henan University of Science and Technology(13480027) to Q. C.the Key Science Foundation of Nanjing Medical University(2015NJMUZD002)+2 种基金the Natural Science Foundation of Higher Education Institutions of Jiangsu Province(16KJB-180020)Natural Science Foundation of Jiangsu Province (BK20171053)National Natural Science Funds of China (81702747) to C.L
文摘Kruppel-like factor 4（Klf4） is a zinc finger transcription factor and plays crucial roles in Xenopus embryogenesis.However, its regulation during embryogenesis is still unclear. Here, we report that Tcf711, a key downstream transducer of the Wnt signaling pathway, could promote Klf4 transcription and stimulate Klf4 promoter activity in early Xenopus embryos. Furthermore, cycloheximide treatment showed a direct effect on Klf4 transcription facilitated by Tcf711. Moreover, the dominant negative form of Tcf711（dnTcf711）, which lacks N-terminus of the β-catenin binding motif, could still activate Klf4 transcription, suggesting that this regulation is Wnt/β-catenin independent.Taken together, our results demonstrate that Tcf711 lies upstream of Klf4 to maintain its expression level during Xenopus embryogenesis.
文摘Both the Wnt/β-catenin and Bone morphogenetic protein （Bmp） signaling pathways play critical roles in dorsal-ventral patterning of the Xenopus embryos. The lymphoid enhancer binding factor （Lef） / T cell factor （Tcf） have been viewed as dedicated transcription factors of the Wnt/β-catenin signaling pathway that are activated by β-catenin binding. Now a Xenopus ventral specific transcription factor Xom has also been identified to bear transactivation activity by binding to Lef/Tcf factors [1].
文摘the left-behind children is appeared in our city in the process, there are many factors that influence the well-being, in this paper I conducted about the influence of left-behind children happiness questionnaire, focuses on the analysis of the influence factors from three aspects of environmental factors, personality factors and social factors. Based on the analys：is results, put forward and strengthen left-behind chi]dren well-being measures.
基金supported by the German Research Council(Deutsche Forschungsgemeinschaft,HA3309/3-1/2,HA3309/6-1,HA3309/7-1)。
文摘Skeletal muscles are essential for locomotion,posture,and metabolic regulation.To understand physiological processes,exercise adaptation,and muscle-related disorders,it is critical to understand the molecular pathways that underlie skeletal muscle function.The process of muscle contra ction,orchestrated by a complex interplay of molecular events,is at the core of skeletal muscle function.Muscle contraction is initiated by an action potential and neuromuscular transmission requiring a neuromuscular junction.Within muscle fibers,calcium ions play a critical role in mediating the interaction between actin and myosin filaments that generate force.Regulation of calcium release from the sarcoplasmic reticulum plays a key role in excitation-contraction coupling.The development and growth of skeletal muscle are regulated by a network of molecular pathways collectively known as myogenesis.Myogenic regulators coordinate the diffe rentiation of myoblasts into mature muscle fibers.Signaling pathways regulate muscle protein synthesis and hypertrophy in response to mechanical stimuli and nutrient availability.Seve ral muscle-related diseases,including congenital myasthenic disorders,sarcopenia,muscular dystrophies,and metabolic myopathies,are underpinned by dys regulated molecular pathways in skeletal muscle.Therapeutic interventions aimed at preserving muscle mass and function,enhancing regeneration,and improving metabolic health hold promise by targeting specific molecular pathways.Other molecular signaling pathways in skeletal muscle include the canonical Wnt signaling pathway,a critical regulator of myogenesis,muscle regeneration,and metabolic function,and the Hippo signaling pathway.In recent years,more details have been uncovered about the role of these two pathways during myogenesis and in developing and adult skeletal muscle fibers,and at the neuromuscular junction.In fact,research in the last few years now suggests that these two signaling pathways are interconnected and that they jointly control physiological and pathophysiological processes in muscle fibers.In this review,we will summarize and discuss the data on these two pathways,focusing on their concerted action next to their contribution to skeletal muscle biology.However,an in-depth discussion of the noncanonical Wnt pathway,the fibro/a dipogenic precursors,or the mechanosensory aspects of these pathways is not the focus of this review.
基金the Diabetes Special Fund Project of Hubei University of Science and Technology(2016-18XZ12)。
文摘[Objectives]This study was conducted to investigate characteristics of the human TCF7 L2 gene promoter.[Methods]The 2000 bp sequence of the 5’regulatory region of the human TCF7 L2 gene was obtained from the UCSC genome database.The promoter,transcription factor binding sites,CpG islands,SNPs and so on were analyzed by a variety of online softwares.[Results]The bioinformatics analysis results showed there were at least 5 potential promoters in the positive-sense strand of the 2000 bp sequence,among which-242--192 bp,-853--803 bp might contain core promoters.A TATA box and a CpG island with a length of 499 bp were found.241,944 and 1035(positive-sense strand)transcription factor binding sites were predicted by the AliBaba2.1,PROMO and JASPAR softwares,respectively.207 common transcription factor binding sites in the conserved region of human and mouse homologous TCF7 L2 gene promoter were identified with CONREAL program,involving 66 kinds of transcription factors.Two SNPs were found in the promoter region.[Conclusions]The promoter of the human TCF7 L2 gene was analyzed by bioinformatics,and the promoter characteristics were obtained.
