RAT-LIVER CYTOSOLIC 4-S POLYCYCLIC AROMATIC HYDROCARBON-BINDING PROTEIN IS GLYCINE N-METHYLTRANSFERASE

In the rat, cytochrome P-450IA1 gene expression, which is most closely associated with aryl hydrocarbon hydroxylase activity, is thought to be regulated by several trans-acting factors, including the 4 S polycy clic aromatic hydrocarbon (PAH)-binding protein. This protein has been purified to homogeneity from rat liver using ion exchange, gel permea tion, hydrophobic interaction, and affinity chromatographies. Partial sequencing of the 33-kDa band indicated its identity as glycine N-meth yltransferase (GNMT). Polyclonal antibodies to GNMT immunoprecipitated PAH-binding activity from rat liver cytosol. Methyltransferase and PA H-binding activities copurified during the course of protein purificat ion. GNMT protein and PAH binding activity were co localized in variou s cytosolic fractions. These data all indicate that the 4 S PAH-bindin g protein and GNMT are one and the same protein or very similar protei ns. Western blot analyses yielded a positive signal under denaturing ( 33 kDa) and nondenaturing (150 kDa, tetramer) conditions; the PAH-bind ing protein also was an oligomer, GNMT was detected by immunohistochem istry in nuclei from H4IIE rat hepatoma cells and rat liver. The local ization of GNMT in liver nuclei is in accordance with a role in modula ting cytochrome P-450IA1 gene expression.