A SWI2/SNF2-type ATPase/helicase protein, mDomino, interacts with myeloid zinc finger protein 2A (MZF-2A) to regulate its transcriptional activity.
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.
Ogawa
Hironori
H
Department of Genetics B-3, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
Ueda
Takeshi
T
Aoyama
Tomohisa
T
Aronheim
Ami
A
Nagata
Shigekazu
S
Fukunaga
Rikiro
R
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D004265:DNA Helicases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D008969:Molecular Sequence Data; D022423:Myeloid Cells / Q000378:metabolism; D009687:Nuclear Proteins; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D015003:Yeasts / Q000235:genetics
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D051741:Kruppel-Like Transcription Factors; C085969:MZF1 protein, human; C490095:Mzf1 protein, mouse; D009687:Nuclear Proteins; C084011:SMARCA2 protein, human; C499503:Smarca2 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C499600:dom protein, Drosophila; D000251:Adenosine Triphosphatases; C084108:SMARCA4 protein, human; C513194:Smarca4 protein, mouse; D004265:DNA Helicases; C499332:Ep400 protein, mouse