Characterization of mouse metastasis-associated gene 2: genomic structure, nuclear localization signal, and alternative potentials as transcriptional activator and repressor.
We characterized the mouse metastasis-associated gene 2 product (mmta2), which is a homolog of the metastasis-associated gene 1 product (MTA1). We revealed that the mmta2 gene spanned approximately 10 kb and was separated into 18 exons. The transcription start site of mmta2 was located 377 bp upstream from the putative initiation codon. The subcellular location of the mmta2 protein was the nucleus, and nuclear localization signals were identified in the region between amino acids 456 and 497. To obtain data on the transcription-regulating potential of mmta2, various constructs containing different portions were fused to the GAL4 DNA-binding domain. The entire mmta2 protein repressed the transcription of the reporter genes, whereas treatment with a histone deacetylase inhibitor, trichostatin A (TSA), led to recovery from the repression and to transcriptional activation. However, the N terminus of mmta2 activated transcriptional activity in the absence of TSA. These results suggest that mmta2 has the potential to both repress and activate gene transcription and that its transcription repression activity might be related to histone deacetylation.
Matsusue
K
K
Laboratory of Metabolism, U.S. National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Takiguchi
S
S
Toh
Y
Y
Kono
A
A
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D018387:Codon, Initiator / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005091:Exons; D015870:Gene Expression; D016678:Genome; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis / Q000235:genetics*; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*
D002352:Carrier Proteins; D018387:Codon, Initiator; D018076:DNA, Complementary; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C089320:MTA1 protein, human; C529798:Mta2 protein, mouse; D019913:Nuclear Localization Signals; D011506:Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; C012589:trichostatin A; C120917:MTA2 protein, human; D006655:Histone Deacetylases