A NOVEL DNA-BINDING PROTEIN THAT RECOGNIZES THE METHYLATED C-MYC BINDING MOTIF

We detected a novel nuclear protein, MMBP-3, that bound to the c-Myc b inding motif (CACGTG) in which deoxycytidine in the CpG sequence was m ethylated. MMBP-3 was partially purified by chromatography on heparin- agarose and hydroxyapatite, followed by affinity adsorption to a matri x coupled to the methylated binding motif, Its binding to the methylat ed c-Myc binding motif was specific, although it also recognized the u nmethylated motif weakly, MMBP-3 was further found to recognize only o ne of two differently hemimethylated forms of the double-stranded c-My c binding motif, MMBP-3 activity was detected in proliferating C2C12 a nd C3H/10T1/2 cells, and down regulated when the growth of these cells was inhibited, We propose that MMBP-3 plays a role in regulating the c-Myc function by recognizing the methylation state of the c-Myc bindi ng motif in a growth-dependent manner.