HIPK2 can simultaneously phosphorylate RUNX1 and EP300 (p300) histone acetyltransferase bound to the RUNX1:CBFB complex. RUNX1 is phosphorylated by HIPK2 at serine residues S249 and S273 and threonine residue T276. EP300 is phosphorylated by HIPK2 at multiple serine and threonine residues that have not been thoroughly identified. HIPK2-mediated phosphorylation contributed to the activation of histone acetyltransferase activity of EP300 at RUNX1 target promoters (Aikawa et al. 2006, Wee et al. 2008).