Mga, a dual-specificity transcription factor that interacts with Max and contains a T-domain DNA-binding motif

The basic-helix-loop-helix-leucine zipper (bHLHZip) proteins Myc, Mad and M nt are part of a transcription activation/repression system involved in the regulation of cell proliferation, The function of these proteins as transc ription factors is mediated by heterodimerization with the small bHLHZip pr otein Max, which is required for their specific DNA binding to E-box sequen ces. We have identified a novel Max-interacting protein, Mga, which contain s a Myc-like bHLHZip motif, but otherwise shows no relationship with Mac or other Max-interacting proteins, Like Myc, Mad and Mnt proteins, Mga requir es heterodimerization with Max for binding to the preferred Myc-Max-binding site CACGTG, In addition to the bHLHZip domain, Mga contains a second DNA- binding domain: the T-box or T-domain, The T-domain is a highly conserved D NA-binding motif originally defined in Brachyury and characteristic of the Tbx family of transcription factors. Mga binds the preferred Brachyury-bind ing sequence and represses transcription of reporter genes containing promo ter-proximal Brachyury-binding sites. Surprisingly, Mga is converted to a t ranscription activator of both Myc-Max and Brachyury site-containing report ers in a Max-dependent manner. Our results suggest that Mga functions as a dual-specificity transcription factor that regulates the expression of both Max-network and T-box family target genes.