PITX2 associates with PTIP-containing histone H3 lysine 4 methyltransferase complex

Biochem Biophys Res Commun. 2014 Feb 21;444(4):634-7. doi: 10.1016/j.bbrc.2014.01.143. Epub 2014 Jan 31.

Abstract

Pituitary homeobox 2 (PITX2), a Paired-like homeodomain transcription factor and a downstream effector of Wnt/β-catenin signaling, plays substantial roles in embryonic development and human disorders. The mechanism of its functions, however, is not fully understood. In this study, we demonstrated that PITX2 associated with histone H3 lysine 4 (H3K4) methyltransferase (HKMT) mixed-lineage leukemia 4 (MLL4/KMT2D), Pax transactivation domain-interacting protein (PTIP), and other H3K4·HKMT core subunits. This association of PITX2 with H3K4·HKMT complex was dependent on PITX2's homeodomain. Consistently, the PITX2 protein complex was shown to possess H3K4·HKMT activity. Furthermore, the chromatin immunoprecipitation result revealed co-occupancy of PITX2 and PTIP on the promoter of the PITX2's transcriptional target. Taken together, our data provide new mechanistic perspectives on PITX2's functions and its related biological processes.

Keywords: Histone H3 lysine 4 (H3K4); Histone lysine methyltransferase (HKMT); MLL4/KMT2D; PITX2; PTIP.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Carrier Proteins / analysis
  • Carrier Proteins / metabolism*
  • DNA-Binding Proteins / metabolism
  • HEK293 Cells
  • Histone-Lysine N-Methyltransferase / analysis
  • Histone-Lysine N-Methyltransferase / metabolism*
  • Histones / metabolism
  • Homeobox Protein PITX2
  • Homeodomain Proteins / analysis
  • Homeodomain Proteins / metabolism*
  • Humans
  • Nuclear Proteins / analysis
  • Nuclear Proteins / metabolism*
  • Promoter Regions, Genetic
  • Protein Interaction Maps
  • Transcription Factors / analysis
  • Transcription Factors / metabolism*

Substances

  • ASH2L protein, human
  • Carrier Proteins
  • DNA-Binding Proteins
  • Histones
  • Homeodomain Proteins
  • Nuclear Proteins
  • PAXIP1 protein, human
  • RBBP5 protein, human
  • Transcription Factors
  • Histone-Lysine N-Methyltransferase
  • MLL4 protein, human