Involved in the transcriptional regulation of genes required for mesoderm formation and differentiation. Binds to a palindromic site (called T site) and activates gene transcription when bound to such a site.
Interacting selectively and non-covalently with an RNA polymerase II transcription activating factor, a protein involved in positive regulation of transcription.
Evidence
1:
Inferred from Physical InteractionBHF-UCL
Mixl1 is a homeodomain transcription factor required for mesoderm and endoderm patterning during mammalian embryogenesis. Despite its crucial function in development, co-factors that modulate the activity of Mixl1 remain poorly defined. Here we report that Mixl1 interacts physically and functionally with the T-box protein Brachyury and related members of the T-box family of transcription factors. Transcriptional and protein analyses demonstrated overlapping expression of Mixl1 and Brachyury during embryonic stem cell differentiation. In vitro protein interaction studies showed that the Mixl1 with Brachyury associated via their DNA-binding domains and gel shift assays revealed that the Brachyury T-box domain bound to Mixl1-DNA complexes. Furthermore, luciferase reporter experiments indicated that association of Mixl1 with Brachyury and related T-box factors inhibited the transactivating potential of Mixl1 on the Gsc and Pdgfrα promoters. Our results indicate that the activity of Mixl1 can be modulated by protein-protein interactions and that T-box factors can function as negative regulators of Mixl1 activity.
Interacting selectively and non-covalently with a RNA polymerase II (Pol II) distal enhancer. In mammalian cells, enhancers are distal sequences that increase the utilization of some promoters, and can function in either orientation and in any location (upstream or downstream) relative to the core promoter.
Our recent work demonstrated that common cardiovascular progenitor cells are characterized and induced by the expression of the transcription factor mesoderm posterior1 (MesP1) in vertebrate embryos and murine embryonic stem cells. As the proliferative potential of stem cell-derived cardiomyocytes is limited, it is crucial to understand how MesP1 expression is mediated in order to achieve reasonable and reliable yields for novel stem cell-based therapeutic options. As potential upstream regulators of MesP1, we therefore analysed Eomes and Brachyury(T), which had been controversially discussed as being crucial for cardiovasculogenic lineage formation.
RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activitydefinition[GO:0003705]
Interacting selectively and non-covalently with a sequence of DNA that is in a distal enhancer region for RNA polymerase II (RNAP II) in order to modulate transcription by RNAP II.
Our recent work demonstrated that common cardiovascular progenitor cells are characterized and induced by the expression of the transcription factor mesoderm posterior1 (MesP1) in vertebrate embryos and murine embryonic stem cells. As the proliferative potential of stem cell-derived cardiomyocytes is limited, it is crucial to understand how MesP1 expression is mediated in order to achieve reasonable and reliable yields for novel stem cell-based therapeutic options. As potential upstream regulators of MesP1, we therefore analysed Eomes and Brachyury(T), which had been controversially discussed as being crucial for cardiovasculogenic lineage formation.
Interacting selectively and non-covalently with an RNA polymerase II transcription factor, any protein required to initiate or regulate transcription by RNA polymerase II.
ISSOrtholog Curator
RNA polymerase II transcription factor binding transcription factor activity involved in negative regulation of transcriptiondefinition[GO:0001191]
Interacting selectively and non-covalently with an RNA polymerase II transcription factor, which may be a single protein or a complex, in order to stop, prevent, or reduce the frequency, rate or extent of transcription from an RNA polymerase II promoter. A protein binding transcription factor may or may not also interact with the template nucleic acid (either DNA or RNA) as well.
Interacting selectively and non-covalently with a specific DNA sequence in order to modulate transcription. The transcription factor may or may not also interact selectively with a protein or macromolecular complex.
We have cloned the human gene encoding the transcription factor T. T protein is vital for the formation of posterior mesoderm and axial development in all vertebrates. Brachyury mutant mice, which lack T protein, die in utero with abnormal notochord, posterior somites, and allantois. We have identified human T genomic clones and derived the mRNA sequence and gene structure. There is 91% amino acid identity between human and mouse T proteins overall and complete identity across 77 amino acids of the T-box motif within the DNA-binding domain. Human T expression is very similar to that found for T in other vertebrate species and is confined to cells derived from the notochord. The human T gene maps to chromosome 6q27 and is only the second human member of the T-box gene family to be described.
We have cloned the human gene encoding the transcription factor T. T protein is vital for the formation of posterior mesoderm and axial development in all vertebrates. Brachyury mutant mice, which lack T protein, die in utero with abnormal notochord, posterior somites, and allantois. We have identified human T genomic clones and derived the mRNA sequence and gene structure. There is 91% amino acid identity between human and mouse T proteins overall and complete identity across 77 amino acids of the T-box motif within the DNA-binding domain. Human T expression is very similar to that found for T in other vertebrate species and is confined to cells derived from the notochord. The human T gene maps to chromosome 6q27 and is only the second human member of the T-box gene family to be described.
A series of molecular signals initiated by the binding of a member of the BMP (bone morphogenetic protein) family to a receptor on the surface of a target cell, and ending with regulation of a downstream cellular process, e.g. transcription.
The series of molecular signals initiated by binding of a Wnt protein to a frizzled family receptor on the surface of the target cell, followed by propagation of the signal via beta-catenin, and ending with a change in transcription of target genes. In this pathway, the activated receptor signals via downstream effectors that result in the inhibition of beta-catenin phosphorylation, thereby preventing degradation of beta-catenin. Stabilized beta-catenin can then accumulate and travel to the nucleus to trigger changes in transcription of target genes.
The process in which a cardiac muscle precursor cell acquires specialized features of a cardiac muscle cell. Cardiac muscle cells are striated muscle cells that are responsible for heart contraction.
The process, occurring during the embryonic phase, whose specific outcome is the progression of the skeleton over time, from its formation to the mature structure.
The developmental process in which the heart is generated and organized. The heart is a hollow, muscular organ, which, by contracting rhythmically, keeps up the circulation of the blood.
Our recent work demonstrated that common cardiovascular progenitor cells are characterized and induced by the expression of the transcription factor mesoderm posterior1 (MesP1) in vertebrate embryos and murine embryonic stem cells. As the proliferative potential of stem cell-derived cardiomyocytes is limited, it is crucial to understand how MesP1 expression is mediated in order to achieve reasonable and reliable yields for novel stem cell-based therapeutic options. As potential upstream regulators of MesP1, we therefore analysed Eomes and Brachyury(T), which had been controversially discussed as being crucial for cardiovasculogenic lineage formation.
The process whose specific outcome is the progression of the mesoderm over time, from its formation to the mature structure. The mesoderm is the middle germ layer that develops into muscle, bone, cartilage, blood and connective tissue.
We have cloned the human gene encoding the transcription factor T. T protein is vital for the formation of posterior mesoderm and axial development in all vertebrates. Brachyury mutant mice, which lack T protein, die in utero with abnormal notochord, posterior somites, and allantois. We have identified human T genomic clones and derived the mRNA sequence and gene structure. There is 91% amino acid identity between human and mouse T proteins overall and complete identity across 77 amino acids of the T-box motif within the DNA-binding domain. Human T expression is very similar to that found for T in other vertebrate species and is confined to cells derived from the notochord. The human T gene maps to chromosome 6q27 and is only the second human member of the T-box gene family to be described.
The process in which the anatomical structures of the neural plate are generated and organized. The neural plate is a specialized region of columnar epithelial cells in the dorsal ectoderm that will give rise to nervous system tissue.
The formation of the notochord from the chordamesoderm. The notochord is composed of large cells packed within a firm connective tissue sheath and is found in all chordates at the ventral surface of the neural tube. In vertebrates, the notochord contributes to the vertebral column.
The infiltration by sperm of the zona pellucida to reach the oocyte. The process involves digestive enzymes from a modified lysosome called the acrosome, situated at the head of the sperm.
Any process that activates or increases the rate or extent of cell proliferation.
IEAOrtholog Compara
Positive regulation of transcription from RNA polymerase II promoter involved in myocardial precursor cell differentiationdefinition[GO:0003257]
Any process that increases the frequency, rate or extent of transcription from an RNA polymerase II promoter that contributes to the differentiation of a myocardial precursor cell.
Our recent work demonstrated that common cardiovascular progenitor cells are characterized and induced by the expression of the transcription factor mesoderm posterior1 (MesP1) in vertebrate embryos and murine embryonic stem cells. As the proliferative potential of stem cell-derived cardiomyocytes is limited, it is crucial to understand how MesP1 expression is mediated in order to achieve reasonable and reliable yields for novel stem cell-based therapeutic options. As potential upstream regulators of MesP1, we therefore analysed Eomes and Brachyury(T), which had been controversially discussed as being crucial for cardiovasculogenic lineage formation.
The process in which a post-anal tail is generated and organized. A post-anal tail is a muscular region of the body that extends posterior to the anus. The post-anal tail may aid locomotion and balance.
The developmental process pertaining to the initial formation of the primitive streak from unspecified parts. The primitive streak is a ridge of cells running along the midline of the embryo where the mesoderm ingresses. It defines the anterior-posterior axis.
During embryonic development, multipotent cardiovascular progenitor cells are specified from early mesoderm. Using mouse ESCs in which gene expression can be temporally regulated, we have found that transient expression of Mesp1 dramatically accelerates and enhances multipotent cardiovascular progenitor specification through an intrinsic and cell autonomous mechanism. Genome-wide transcriptional analysis indicates that Mesp1 rapidly activates and represses a discrete set of genes, and chromatin immunoprecipitation shows that Mesp1 directly binds to regulatory DNA sequences located in the promoter of many key genes in the core cardiac transcriptional machinery, resulting in their rapid upregulation. Mesp1 also directly represses the expression of key genes regulating other early mesoderm and endoderm cell fates. Our results demonstrate that Mesp1 acts as a key regulatory switch during cardiovascular specification, residing at the top of the hierarchy of the gene network responsible for cardiovascular cell-fate determination.
The cellular process in which a signal is conveyed to trigger a change in the activity or state of a cell. Signal transduction begins with reception of a signal (e.g. a ligand binding to a receptor or receptor activation by a stimulus such as light), or for signal transduction in the absence of ligand, signal-withdrawal or the activity of a constitutively active receptor. Signal transduction ends with regulation of a downstream cellular process, e.g. regulation of transcription or regulation of a metabolic process. Signal transduction covers signaling from receptors located on the surface of the cell and signaling via molecules located within the cell. For signaling between cells, signal transduction is restricted to events at and within the receiving cell.
We have cloned the human gene encoding the transcription factor T. T protein is vital for the formation of posterior mesoderm and axial development in all vertebrates. Brachyury mutant mice, which lack T protein, die in utero with abnormal notochord, posterior somites, and allantois. We have identified human T genomic clones and derived the mRNA sequence and gene structure. There is 91% amino acid identity between human and mouse T proteins overall and complete identity across 77 amino acids of the T-box motif within the DNA-binding domain. Human T expression is very similar to that found for T in other vertebrate species and is confined to cells derived from the notochord. The human T gene maps to chromosome 6q27 and is only the second human member of the T-box gene family to be described.
Signal transduction involved in regulation of gene expressiondefinition[GO:0023019]‹silver
Any process that modulates the frequency, rate or extent of gene expression as a consequence of a process in which a signal is released and/or conveyed from one location to another.
The cascade of processes by which a signal interacts with a receptor, causing a change in the activity of a SMAD protein, and ultimately effecting a change in the functioning of the cell.
Protein involved in the transfer of genetic information from DNA to messenger RNA (mRNA) by DNA-directed RNA polymerase. In the case of some RNA viruses, protein involved in the transfer of genetic information from RNA to messenger RNA (mRNA) by RNA-directed RNA polymerase.
Protein involved in development, the process whereby a multicellular organism develops from its early immature forms, e.g., zygote, larva, embryo, into an adult.
A reference proteome is a set of protein sequences derived from a complete proteome which constitutes a defined standard for a particular user community. Reference proteomes are manually defined according to a number of criteria. They cover the proteomes of well- studied model organisms and other proteomes of interest for biomedical and biotechnological research. Reference proteomes have been selected to provide broad coverage of the tree of life, and constitute a representative cross-section of the taxonomic diversity to be found within UniProtKB.
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