Characterization of mouse metastasis-associated gene 2: Genomic structure,nuclear localization signal, and alternative potentials as transcriptionalactivator and repressor

We characterized the mouse metastasis-associated gene 2 product (mmta2), wh ich is a homolog of the metastasis-associated gene I product (MTA1). We rev ealed that the mmta2 gene spanned approximately 10 kb and was separated int o 18 exons. The transcription start site of mmta2 was located 377 bp upstre am from the putative initiation codon. The subcellular location of the mmta 2 protein was the nucleus, and nuclear localization signals were identified in the region between amino acids 456 and 497. To obtain data on the trans cription-regulating potential of mmta2, various constructs containing diffe rent portions were fused to the GAL4 DNA-binding domain. The entire mmta2 p rotein repressed the transcription of the reporter genes, whereas treatment with a histone deacetylase inhibitor, trichostatin A (TSA), led to recover y from the repression and to transcriptional activation. However, the N ter minus of mmta2 activated transcriptional activity in the absence of TSA. Th ese results suggest that mmta2 has the potential to both repress and activa te gene transcription and that its transcription repression activity might be related to histone deacetylation.