Neural-specific expression, genomic structure, and chromosomal localization of the gene encoding the zinc-finger transcription factor NGFI-C.
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.
Crosby
S D
SD
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.
Veile
R A
RA
Donis-Keller
H
H
Baraban
J M
JM
Bhat
R V
RV
Simburger
K S
KS
Milbrandt
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000502:physiology* / Q000503:physiopathology; D002871:Chromosome Banding; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D004268:DNA-Binding Proteins / Q000235:genetics*; D015698:Genomic Library; D006801:Humans; D007621:Karyotyping; D008297:Male; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D009928:Organ Specificity; D016716:PC12 Cells; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012640:Seizures / Q000503:physiopathology; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics*
D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D014157:Transcription Factors