In vivo role of different domains and of phosphorylation in the transcription factor Nkx2-1
Copyright policy )In vivo role of different domains and of phosphorylation in the transcription factor Nkx2-1
Abstract Background The transcription factor Nkx2-1 (also known as TTF-1, Titf1 or T/EBP) contains two apparently redundant activation domains and is post-translationally modified by phosphorylation. We have generated mouse mutant strains to assess the roles of the two activation domains and of phosphorylation in mouse development and differentiation. Results Mouse strains expressing variants of the transcription factor Nkx2-1 deleted of either activation domain have been constructed. Phenotypic analysis shows for each mutant a distinct set of defects demonstrating that distinct portions of the protein endow diverse developmental functions of Nkx2-1. Furthermore, a mouse strain expressing a Nkx2-1 protein mutated in the phosphorylation sites shows a thyroid gland with deranged follicular organization and gene expression profile demonstrating the functional role of phosphorylation in Nkx2-1. Conclusions The pleiotropic functions of Nkx2-1 are not all due to the protein as a whole since some of them can be assigned to separate domains of the protein or to specific post-translational modifications. These results have implication for the evolutionary role of mutations in transcription factors.
Genotype, Fluorescent Antibody Technique, Mice, Transgenic, Animals; Cell Differentiation; Fluorescent Antibody Technique; Gene Expression Profiling; Gene Knock-In Techniques; Gene Knockout Techniques; Genotype; In Situ Hybridization; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mutation; Nuclear Proteins; Oligonucleotide Array Sequence Analysis; Phenotype; Phosphorylation; Pituitary Gland; Protein Structure, Tertiary; Sequence Deletion; Structure-Activity Relationship; Thyroid Gland; Thyroid Nuclear Factor 1; Transcription Factors; Protein Processing, Post-Translational; Developmental Biology, Gene Knockout Techniques, Mice, transcription factors, In vivo; phosphorylation;Nkx2-1., Animals, Gene Knock-In Techniques, Phosphorylation, In Situ Hybridization, Oligonucleotide Array Sequence Analysis, Sequence Deletion, phosphorylation, Gene Expression Profiling, Nuclear Proteins, Cell Differentiation, Embryonic development; transcription factors; phosphorylation, Protein Structure, Tertiary, Mice, Inbred C57BL, Phenotype, Pituitary Gland, Embryonic development, Mutation, Protein Processing, Post-Translational, Developmental Biology, Research Article
Genotype, Fluorescent Antibody Technique, Mice, Transgenic, Animals; Cell Differentiation; Fluorescent Antibody Technique; Gene Expression Profiling; Gene Knock-In Techniques; Gene Knockout Techniques; Genotype; In Situ Hybridization; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mutation; Nuclear Proteins; Oligonucleotide Array Sequence Analysis; Phenotype; Phosphorylation; Pituitary Gland; Protein Structure, Tertiary; Sequence Deletion; Structure-Activity Relationship; Thyroid Gland; Thyroid Nuclear Factor 1; Transcription Factors; Protein Processing, Post-Translational; Developmental Biology, Gene Knockout Techniques, Mice, transcription factors, In vivo; phosphorylation;Nkx2-1., Animals, Gene Knock-In Techniques, Phosphorylation, In Situ Hybridization, Oligonucleotide Array Sequence Analysis, Sequence Deletion, phosphorylation, Gene Expression Profiling, Nuclear Proteins, Cell Differentiation, Embryonic development; transcription factors; phosphorylation, Protein Structure, Tertiary, Mice, Inbred C57BL, Phenotype, Pituitary Gland, Embryonic development, Mutation, Protein Processing, Post-Translational, Developmental Biology, Research Article
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