NeuroD1/E47 regulates the E-box element of a novel zinc finger transcription factor, IA-1, in developing nervous system.
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.
Breslin
Mary B
MB
Research Institute for Children, Children's Hospital, Department of Pediatrics, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70118, USA.
Zhu
Min
M
Lan
Michael S
MS
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D015152:Blotting, Northern; D015139:Blotting, Southern; D001921:Brain / Q000196:embryology*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000502:physiology*; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D017353:Gene Deletion; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009420:Nervous System / Q000196:embryology*; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000737:chemistry*; D013997:Time Factors; D015534:Trans-Activators / Q000502:physiology*; D014158:Transcription, Genetic; D019076:Transgenes; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers; D001616:beta-Galactosidase / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D001616:beta-Galactosidase; C093970:NEUROD1 protein, human; C501008:Neurod1 protein, mouse; C087342:INSM1 protein, human