The nerve growth factor-induced clone C (NGFI-C) gene encodes a zinc-finger transcription factor that is rapidly induced by nerve growth factor in rat pheochromocytoma PC12 cells and by seizure in brain. NGFI-C is closely related to the previously described early response genes, nerve growth factor-induced clone A (NGFI-A or EGR1), EGR2, and EGR3. These four early response (immediate early) proteins all contain very similar zinc-finger DNA binding domains; in addition, analysis of the non-zinc-finger region revealed that they share an additional five highly homologous subdomains, four of which are within the amino terminus. The 5' flanking region of NGFI-C contains several cAMP response elements but does not contain any serum-response elements or CArG boxes [CC(A/T)6GG], cis-acting elements commonly involved in early response gene regulation. NGFI-C mRNA was detected in neural tissues of postnatal animals, but no expression was found in rat embryos. In situ hybridization demonstrated that NGFI-C is rapidly induced in the dentate gyrus of the hippocampus after seizure, but in contrast to NGFI-A, increases in NGFI-C mRNA were not detected in the overlying cortex. By using fluorescence in situ hybridization, NGFI-C was localized to human chromosome 2p13. This region contains a constitutive fragile site that is associated with chromosomal breakpoints and translocations characteristic of some chronic lymphocytic leukemias.