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.
Patel
Sanjeevkumar R
SR
Department of Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
Kim
Doyeob
D
Levitan
Inna
I
Dressler
Gregory R
GR
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D004268:DNA-Binding Proteins; D044127:Epigenesis, Genetic; D054262:Gastrulation; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D051762:PAX2 Transcription Factor / Q000378:metabolism*; D011485:Protein Binding; D011496:Protein Methyltransferases; D017434:Protein Structure, Tertiary
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006657:Histones; D009687:Nuclear Proteins; D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human; C485876:PAXIP1 protein, human; D000076983:Histone Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine