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Originally published In Press as doi:10.1074/jbc.M306795200 on July 30, 2003

J. Biol. Chem., Vol. 278, Issue 40, 38991-38997, October 3, 2003
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NeuroD1/E47 Regulates the E-box Element of a Novel Zinc Finger Transcription Factor, IA-1, in Developing Nervous System*

Mary B. Breslin, Min Zhu {ddagger} and Michael S. Lan §

From the Research Institute for Children, Children's Hospital, Department of Pediatrics, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70118

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 (~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.


Received for publication, June 25, 2003 , and in revised form, July 29, 2003.

* This work was supported by Juvenile Diabetes Research Foundation Grant 1-1999-61 and NIDDK, National Institutes of Health (NIH), Grant DK61436 (to M. S. L.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

{ddagger} Present address: Laboratory of Experimental Gerontology, NIA, NIH, Baltimore, MD 21224.

§ To whom correspondence should be addressed: Research Institute for Children, Children's Hospital, 200 Henry Clay Ave., Research and Education Building, Rm. 2211, New Orleans, LA 70118. Tel.: 504-896-2705; Fax: 504-896-2722; E-mail: mlan{at}chnola-research.org.


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