Background: The myeloid zinc finger protein 2A (MZF‐2A) is a Krüppel‐type C₂H₂ zinc finger transcription factor expressed in myeloid cells and involved in the growth, differentiation and tumorigenesis of myeloid progenitors. Previously we identified a 180 amino acid domain in MZF‐2A which is responsible for the transcriptional activation of MZF‐2A. To understand the mechanism of the MZF‐2A‐dependent transcriptional activation, we screened for molecules that interact with the transactivation domain (TAD) of MZF‐2A.

Results: By using the yeast Ras recruitment two‐hybrid screening, we identified a novel SWI2/SNF2‐related protein, termed mammalian Domino (mDomino), as an MZF‐2A‐binding partner. The mDomino protein, which shows a marked similarity to the Drosophila Domino protein, contains a SWI2/SNF2‐type ATPase/helicase domain, a SANT domain, and a glutamine‐rich (Q‐rich) domain. The C‐terminal Q‐rich domain of mDomino physically associates with the TAD of MZF‐2A in mammalian cells as well as in yeast. Expression of the mDomino Q‐rich domain, together with MZF‐2A in myeloid LGM‐1 cells, enhanced the MZF‐2A‐mediated activation of a reporter gene.

Conclusions: These results strongly suggest that an ATP‐dependent chromatin‐remodelling complex containing mDomino interacts with MZF‐2A to regulate gene expression in myeloid cells.