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The BRCT-domain containing protein PTIP links PAX2 to a histone H3, lysine 4 methyltransferase complex.

The MLL family of histone methyltransferases maintains active chromatin domains by methylating histone H3 on lysine 4 (H3K4). How MLL complexes recognize specific chromatin domains in a temporal and tissue-specific manner remains unclear. We show that the DNA-binding protein PAX2 promotes assembly of an H3K4 methyltransferase complex through the ubiquitously expressed nuclear factor PTIP (pax transcription activation domain interacting protein). PTIP copurifies with ALR, MLL3, and other components of a histone methyltransferase complex. PTIP promotes assembly of the ALR complex and H3K4 methylation at a PAX2-binding DNA element. Without PTIP, Pax2 binds to this element but does not assemble the ALR complex. Embryonic lethal ptip-null mutants and conditional mutants both show reduced levels of methylated H3K4. Thus, PTIP bridges DNA-binding developmental regulators to histone methyltransferase-dependent epigenetic regulation.

Pubmed ID: 17925232

Authors

  • Patel SR
  • Kim D
  • Levitan I
  • Dressler GR

Journal

Developmental cell

Publication Data

October 10, 2007

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK02803
  • Agency: NIDDK NIH HHS, Id: DK039255
  • Agency: NIDDK NIH HHS, Id: DK054740
  • Agency: NIDDK NIH HHS, Id: DK073722
  • Agency: NIDDK NIH HHS, Id: R01 DK054740
  • Agency: NIDDK NIH HHS, Id: R01 DK054740-05
  • Agency: NIDDK NIH HHS, Id: R01 DK054740-05S1
  • Agency: NIDDK NIH HHS, Id: R01 DK054740-06
  • Agency: NIDDK NIH HHS, Id: R01 DK054740-07
  • Agency: NIDDK NIH HHS, Id: R01 DK054740-08
  • Agency: NIDDK NIH HHS, Id: R01 DK073722
  • Agency: NIDDK NIH HHS, Id: R01 DK073722-01A1
  • Agency: NIDDK NIH HHS, Id: R01 DK073722-02

Mesh Terms

  • Animals
  • Carrier Proteins
  • Cell Line
  • Epigenesis, Genetic
  • Gastrulation
  • Histone-Lysine N-Methyltransferase
  • Histones
  • Humans
  • Lysine
  • Methylation
  • Mice
  • Nuclear Proteins
  • PAX2 Transcription Factor
  • Protein Binding
  • Protein Methyltransferases
  • Protein Structure, Tertiary