Human hematopoietic cell specific nuclear protein MNDA interacts with the multifunctional transcription factor YY1...

The human myeloid nuclear differentiation antigen, MNDA, is expressed only in myelomonocytic and a subset of B lymphoid hematopoietic cells. MNDA is uniformly distributed throughout the interphase cell nucleus and associates with chromatin, but does not bind specific DNA sequences. We recently demonstrated that MNDA binds nucleolin and nucleophosmin/NPM/B23 and both of these nuclear proteins bind the ubiquitous zinc finger transcription factor YY1. Investigations of the possible effect of MNDA on the interaction between YY1 and NPM, showed that MNDA bound YY1 directly under both in vitro and in vivo conditions. The MNDA-YY1 interaction enhanced the affinity of YY1 for its target DNA and decreased its rate of dissociation. The N-terminal half (200 amino acids) of MNDA was sufficient for maximum enhancement of YY1 DNA binding and a portion of this sequence was responsible for binding YY1. MNDA participated in a ternary complex with YY1 and the YY1 target DNA element. The results show that MNDA affects the ability of YY1 to bind its target DNA sequnce and that MNDA participates in a ternary complex possibly acting as a cofactor to impart lineage specific features to YY1 function.