NeuroD1/E47 regulates the E-box element of a novel zinc finger transcription factor, IA-1, in developing nervous system.

Breslin MB, Zhu M, Lan MS
J Biol Chem. 2003 278 (40): 38991-7

PMID: 12890672 · PMCID: PMC1236987 · DOI:10.1074/jbc.M306795200

IA-1 is a novel zinc finger transcription factor with a restricted tissue distribution in the embryonic nervous system and tumors of neuroendocrine origin. The 1.7-kilobase 5'-upstream DNA sequence of the human IA-1 gene directed transgene expression predominantly in the developing nervous system including forebrain, midbrain, hindbrain, spinal cord, retina, olfactory bulb, and cerebellum, which recapitulated the expression patterns of neuroendocrine tissues and childhood brain tumors. The IA-1 promoter deletion reporter gene constructs revealed that the sequence between -426 and -65 bp containing three putative E-boxes (approximately 361 bp) upstream of the transcription start site was sufficient to confer tissue-specific transcriptional activity. Further mutation analysis revealed that the proximal E-box (E3) closest to the start site is critical to confer transcriptional activity. Electrophoretic mobility shift assay and transient transfection studies demonstrated that the NeuroD1 and E47 heterodimer are the key transcription factors that regulate the proximal E-box of the IA-1 promoter. Therefore, we concluded that the IA-1 gene is developmentally expressed in the nervous system and the NeuroD1/E47 transcription factors up-regulate IA-1 gene expression through the proximal E-box element of the IA-1 promoter.

MeSH Terms (26)

Animals Basic Helix-Loop-Helix Transcription Factors beta-Galactosidase Blotting, Northern Blotting, Southern Brain Dimerization DNA-Binding Proteins DNA Mutational Analysis Dose-Response Relationship, Drug Gene Deletion Genes, Reporter HeLa Cells Humans Immunohistochemistry Mice Mice, Transgenic Nervous System Promoter Regions, Genetic Repressor Proteins Time Factors Trans-Activators Transcription, Genetic Transgenes Tumor Cells, Cultured Zinc Fingers

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