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CXXC finger protein 1 contains redundant functional domains that support embryonic stem cell cytosine methylation, histone methylation, and differentiation.

http://www.ncbi.nlm.nih.gov/pubmed/19433449

CXXC finger protein 1 (Cfp1) is a regulator of both cytosine methylation and histone methylation. Murine embryonic stem (ES) cells lacking Cfp1 exhibit a decreased plating efficiency, decreased cytosine methylation, elevated global levels of histone H3-Lys4 trimethylation, and a failure to differentiate in vitro. Remarkably, transfection studies reveal that expression of either the amino half of Cfp1 (amino acids 1 to 367 [Cfp1(1-367)]) or the carboxyl half of Cfp1 (Cfp1(361-656)) is sufficient to correct all of the defects observed with ES cells that lack Cfp1. However, a point mutation (C169A) that abolishes DNA-binding activity of Cfp1 ablates the rescue activity of the Cfp1(1-367) fragment, and a point mutation (C375A) that abolishes the interaction of Cfp1 with the Setd1 histone H3-Lys4 methyltransferase complexes ablates the rescue activity of the Cfp1(361-656) fragment. Introduction of both the C169A and C375A point mutations ablates the rescue activity of the full-length Cfp1 protein. These results indicate that retention of either the Cfp1 DNA-binding domain or Setd1 interaction domain is required for Cfp1 rescue activity, and they illustrate the functional complexity of this critical epigenetic regulator. A model is presented for how epigenetic cross talk may explain the finding of redundant functional domains within Cfp1.

Pubmed ID: 19433449 RIS Download

Mesh terms: Amino Acid Sequence | Amino Acid Substitution | Animals | Base Sequence | Binding Sites | Cell Differentiation | Cell Line | Cytosine | DNA Methylation | DNA Primers | DNA-Binding Proteins | Embryonic Stem Cells | Epigenesis, Genetic | Histones | Humans | Mice | Mice, Knockout | Models, Biological | Molecular Sequence Data | Mutagenesis, Site-Directed | Peptide Fragments | Protein Structure, Tertiary | Sequence Homology, Amino Acid | Trans-Activators | Transfection

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Associated grants

  • Agency: NIAID NIH HHS, Id: T32 AI060519
  • Agency: NIAID NIH HHS, Id: T32 AI060519

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