Protein complex formation between Msx1 and Lhx2 homeoproteins is incompatible with DNA binding activity

Differentiation. 1998 Jul;63(3):151-7. doi: 10.1046/j.1432-0436.1998.6330151.x.


Msx genes encode a family of homeoproteins that function as transcription repressors through protein-protein interactions. Here we show that Lhx2, a LIM-type homeoprotein, is a protein partner for Msx1 in vitro and in cellular extracts. The interaction between Msx1 and Lhx2 is mediated through the homeodomain-containing regions of both proteins. Interestingly, the LIM domains, which serve as protein interaction domains for other partners of Lhx2, are not required for the Msx1-Lhx2 association. We show that Msx1 and Lhx2 form a protein complex in the absence of DNA, and that DNA binding by either protein alone can occur at the expense of protein complex formation. The significance of this protein-protein interaction is underscored by the expression patterns of Msx1 and Lhx2, which are partially overlapping during murine embryogenesis. The description of Lhx2 as a protein partner for Msx1 suggests that the functional specificity of homeoproteins in vivo is determined by a balance between their association with DNA and their protein partners.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • DNA / metabolism
  • Homeodomain Proteins / metabolism*
  • LIM-Homeodomain Proteins
  • Limb Buds / metabolism
  • MSX1 Transcription Factor
  • Mice
  • Molecular Sequence Data
  • Sequence Homology, Amino Acid
  • Substrate Specificity
  • Transcription Factors / metabolism*


  • Homeodomain Proteins
  • LIM-Homeodomain Proteins
  • Lhx2 protein, mouse
  • MSX1 Transcription Factor
  • Transcription Factors
  • DNA