The NGFI-B gene, a transcriptionally inducible member of the steroid receptor gene superfamily: genomic structure and expression in rat brain after seizure induction.
The NGFI-B cDNA was previously isolated by virtue of its induction by nerve growth factor (NGF) in PC12 cells. It encodes a 61-kilodalton protein that has two regions of extensive homology with members of the steroid/thyroid hormone receptor gene family. The rat NGFI-B gene is approximately 7.6 kilobases long and is interrupted by six introns. Although the exon-intron structure of the gene is similar to those of several other members of the steroid/thyroid hormone receptor gene family, there is a novel splice site within the DNA-binding domain which suggests that NGFI-B constitutes yet another evolutionary digression from a postulated common ancestral receptor gene. Primer extension and S1 nuclease protection assays were used to determine the transcription initiation site, which displayed the heterogeneity typical of genes that lack a TATA box. Sequence analysis of the 5' flanking region revealed several GC boxes but no identifiable TATA box. Four potential AP1 binding sites were identified at nucleotides -49, -78, -222, and -242. Neither the serum response element nor the CArG box element, two sequences found in other growth factor-inducible genes, was detected in this region of the growth factor-inducible NGFI-B gene. Nevertheless, results of nuclear runoff experiments demonstrated that the NGFI-B gene was transcriptionally activated by nerve growth factor in PC12 cells. In vivo, a rapid, dramatic increase in NGFI-B mRNA was observed in the cerebral cortex, midbrain, and cerebellum of animals that experienced a convulsant-induced seizure.
Watson
M A
MA
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
Milbrandt
J
J
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D015870:Gene Expression; D015698:Genomic Library; D007438:Introns / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family; D009414:Nerve Growth Factors / Q000502:physiology*; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D010673:Pheochromocytoma / Q000235:genetics; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D015183:Restriction Mapping; D012640:Seizures / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D009414:Nerve Growth Factors; C539820:Nr4a1 protein, rat; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; D012313:RNA