Based on studies in mice, RUNX2 forms a complex with the histone deacetylase HDAC4. The interaction involves the Runt DNA binding domain of RUNX2 and leads to inhibition of RUNX2 binding to its target DNA sequences. Specifically, interference with RUNX2 binding to the RUNX2 promoter in the presence of HDAC4 has been demonstrated. Hdac4 knockout mice develop premature ossification of developing bones because of premature and ectopic onset of chondrocyte hypertrophy. This phenotype is similar to the Runx2 overexpression phenotype in mouse chondrocytes (Vega et al. 2004).