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PTIP associates with MLL3- and MLL4-containing histone H3 lysine 4 methyltransferase complex.

PTIP, a protein with tandem BRCT domains, has been implicated in DNA damage response. However, its normal cellular functions remain unclear. Here we show that while ectopically expressed PTIP is capable of interacting with DNA damage response proteins including 53BP1, endogenous PTIP, and a novel protein PA1 are both components of a Set1-like histone methyltransferase (HMT) complex that also contains ASH2L, RBBP5, WDR5, hDPY-30, NCOA6, SET domain-containing HMTs MLL3 and MLL4, and substoichiometric amount of JmjC domain-containing putative histone demethylase UTX. PTIP complex carries robust HMT activity and specifically methylates lysine 4 (K4) on histone H3. Furthermore, PA1 binds PTIP directly and requires PTIP for interaction with the rest of the complex. Moreover, we show that hDPY-30 binds ASH2L directly. The evolutionarily conserved hDPY-30, ASH2L, RBBP5, and WDR5 likely constitute a subcomplex that is shared by all human Set1-like HMT complexes. In contrast, PTIP, PA1, and UTX specifically associate with the PTIP complex. Thus, in cells without DNA damage agent treatment, the endogenous PTIP associates with a Set1-like HMT complex of unique subunit composition. As histone H3 K4 methylation associates with active genes, our study suggests a potential role of PTIP in the regulation of gene expression.

Pubmed ID: 17500065

Authors

  • Cho YW
  • Hong T
  • Hong S
  • Guo H
  • Yu H
  • Kim D
  • Guszczynski T
  • Dressler GR
  • Copeland TD
  • Kalkum M
  • Ge K

Journal

The Journal of biological chemistry

Publication Data

July 13, 2007

Associated Grants

  • Agency: Intramural NIH HHS, Id: Z01 DK047055-01
  • Agency: Intramural NIH HHS, Id: Z01 DK075003-04
  • Agency: Intramural NIH HHS, Id: Z99 DK999999
  • Agency: NIDDK NIH HHS, Id: ZIADK047055-03
  • Agency: NIDDK NIH HHS, Id: ZIADK075003-06
  • Agency: NIDDK NIH HHS, Id: ZIADK075017-01

Mesh Terms

  • Animals
  • Carrier Proteins
  • Cell Line, Transformed
  • DNA Damage
  • DNA-Binding Proteins
  • HeLa Cells
  • Histone-Lysine N-Methyltransferase
  • Histones
  • Humans
  • Lysine
  • Methylation
  • Mice
  • Mice, Knockout
  • Multiprotein Complexes
  • Nuclear Proteins
  • Protein Methyltransferases
  • Protein Processing, Post-Translational