In vivo role of different domains and of phosphorylation in the transcription factor Nkx2-1

BMC Dev Biol. 2011 Feb 23:11:9. doi: 10.1186/1471-213X-11-9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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 / chemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Phosphorylation
  • Pituitary Gland / embryology*
  • Protein Processing, Post-Translational*
  • Protein Structure, Tertiary / genetics
  • Sequence Deletion
  • Structure-Activity Relationship
  • Thyroid Gland / abnormalities
  • Thyroid Gland / embryology*
  • Thyroid Nuclear Factor 1
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Nkx2-1 protein, mouse
  • Nuclear Proteins
  • Thyroid Nuclear Factor 1
  • Transcription Factors