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PMID: 2492104 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Structure of the NGFI-A gene and detection of upstream sequences responsible for its transcriptional induction by nerve growth factor.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 86 ·No. 1 ·1989-01-00 ·Pages 377-81

Changelian PS, Feng P, King TC, Milbrandt J

Abstract

The NGFI-A gene encodes a "zinc-finger" protein that is rapidly induced by nerve growth factor (NGF) in PC12 rat pheochromocytoma cells. The complete exon/intron organization and nucleotide sequence of the rat NGFI-A gene have been determined. The gene spans 3789 nucleotides (nt) and is interrupted by a single intron at nt 588. All three zinc-finger DNA-binding domains are contiguously coded for within the 3' exon; this is in contrast to the structure described by others for the Xenopus laevis transcription factor TFIIIA gene. To analyze the transcription of this gene, we have determined the transcription start site and nucleotide sequence of the 5' flanking region. Transfection of PC12 cells with a fragment from the 5' flanking region linked to the chloramphenicol acetyltransferase (CAT) gene revealed that it contains an element which imparts an NGF-inducible phenotype to the normally silent CAT gene. Several regions with homologies to recognizable sequence elements are present in this fragment, including a TATA box at nt -27, serum response elements at nt -84, -106, -370, and -408, a cAMP-responsive element at nt -140, and a transcription factor Sp1-binding site at nt -286. These results establish the genomic structure of this mammalian multifinger protein and demonstrate that an NGF-responsive element lies upstream of the NGFI-A gene.

MeSH Terms
Adrenal Gland Neoplasms Amino Acid Sequence Animals Base Sequence Cell Line DNA-Binding Proteins/biosynthesis,genetics Genes Genes, Regulator/drug effects Metalloproteins/biosynthesis,genetics Molecular Sequence Data Nerve Growth Factors/pharmacology Pheochromocytoma Rats Transcription, Genetic/drug effects Zinc/metabolism
Chemicals
DNA-Binding Proteins Metalloproteins Nerve Growth Factors Zinc
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Changelian P S
Department of Pathology, Washington University School of Medicine, Saint Louis, MO 63110.
Feng P
King T C
Milbrandt J
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33 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.86.1.377
Published
1989-01-00
Pages
377-81
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC286468
Subset
IM
Databases
GENBANK
J04154
External Links
PubMed source DOI: 10.1073/pnas.86.1.377 PMC Full Text View journal details
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