Structure and function of the chromogranin a gene: Clues to evolution and tissue-specific expression

Hong Jiang Wu, David Rozansky, Robert J. Farmer, Bruce M. Gill, Daniel T. O'Connor

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

Chromogranin A is the index member of a family of acidic proteins stored and released throughout the neuroendocrine system with peptide hormones and neurotransmitters. To better understand its functional domains, its evolutionary lineage, and the basis of its tissue-specific pattern of expression, we obtained a mouse chromogranin A cDNA and used it to isolate the chromogranin A gene from the mouse genome. We then characterized the gene's exon/intron structure, and the structure and function of its 5′-regulatory region (promoter/enhancer). The chromogranin A gene was complex, its eight exons and seven introns spanning about 11 kilobase pairs. The eight exons displayed some correspondence to putative functional domains suspected within the cDNA-deduced primary structure of the protein. Three exons also displayed both length and sequence homology to exons in another member of the chromogranin/secretogranin family, chromogranin B, suggesting an evolutionary relationship. A 1.2-kilobase pair genomic fragment just 5′ of the coding region was able to program cell type-specific gene expression in a transfection/reporter system. Both pituitary corticotropes and adrenal chromaffin cells recognized this promoter. The promoter possessed some known consensus transcriptional control elements (TATA box, cyclic AMP-response element, and Sp1 site), but otherwise novel transcriptional control elements seem to be operative. The results suggest that this complex gene is encoded by exon modules with evolutionary links to homologous modules in other chromogranin/ secretogranin protein family members, and that the 5′-flanking region of the gene is sufficient to confer neuroendocrine tissue-specific expression of the chromogranin A gene.

Original languageEnglish (US)
Pages (from-to)13130-13134
Number of pages5
JournalJournal of Biological Chemistry
Volume266
Issue number20
StatePublished - 1991
Externally publishedYes

Fingerprint

Chromogranins
Chromogranin A
Exons
Genes
Tissue
Introns
Chromogranin B
Complementary DNA
Chromaffin Cells
Neurosecretory Systems
TATA Box
Peptide Hormones
5' Flanking Region
Nucleic Acid Regulatory Sequences
Response Elements
Proteins
Sequence Homology
Cyclic AMP
Transfection
Neurotransmitter Agents

ASJC Scopus subject areas

  • Biochemistry

Cite this

Structure and function of the chromogranin a gene : Clues to evolution and tissue-specific expression. / Wu, Hong Jiang; Rozansky, David; Farmer, Robert J.; Gill, Bruce M.; O'Connor, Daniel T.

In: Journal of Biological Chemistry, Vol. 266, No. 20, 1991, p. 13130-13134.

Research output: Contribution to journalArticle

Wu, Hong Jiang ; Rozansky, David ; Farmer, Robert J. ; Gill, Bruce M. ; O'Connor, Daniel T. / Structure and function of the chromogranin a gene : Clues to evolution and tissue-specific expression. In: Journal of Biological Chemistry. 1991 ; Vol. 266, No. 20. pp. 13130-13134.
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