We previously reported that YY-1, a versatile transcription factor, regulates expression of glycophorin gene by binding to its locus control region-like region (Gp-LCR) in combination with E-box binding protein during murine erythroleukemia (MEL) cell differentiation. In the present work, we demonstrated that YY-1 and c-Myc, a nuclear oncoprotein, were physically associated in vivo and that down regulation of c-Myc liberated free YY-1 from its complex, resulting in the functional binding of YY-1 to the Gp-LCR. We also showed that the E-box binding protein (EBP) which bound to E-box was physically associated with YY-1, facilitated binding of YY-1 to the neighboring site and their combinatorial binding may stimulate the GpLCR mediated enhancement of erythroid-specific transcription of glycophorin gene in MEL cells.