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Molecular and Cellular Biology, November 2007, p. 7839-7847, Vol. 27, No. 22
0270-7306/07/$08.00+0     doi:10.1128/MCB.00438-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The Basic Helix-Loop-Helix Transcription Factor NeuroD1 Facilitates Interaction of Sp1 with the Secretin Gene Enhancer{triangledown}

Subir K. Ray and Andrew B. Leiter*

Department of Medicine, Division of Gastroenterology, University of Massachusetts Medical School, Worcester, Massachusetts

Received 14 March 2007/ Returned for modification 24 April 2007/ Accepted 8 September 2007

The basic helix-loop-helix transcription factor NeuroD1 is required for late events in neuronal differentiation, for maturation of pancreatic ß cells, and for terminal differentiation of enteroendocrine cells expressing the hormone secretin. NeuroD1-null mice demonstrated that this protein is essential for expression of the secretin gene in the murine intestine, and yet it is a relatively weak transcriptional activator by itself. The present study shows that Sp1 and NeuroD1 synergistically activate transcription of the secretin gene. NeuroD1, but not its widely expressed dimerization partner E12, physically interacts with the C-terminal 167 amino acids of Sp1, which include its DNA binding zinc fingers. NeuroD1 stabilizes Sp1 DNA binding to an adjacent Sp1 binding site on the promoter to generate a higher-order DNA-protein complex containing both proteins and facilitates Sp1 occupancy of the secretin promoter in vivo. NeuroD-dependent transcription of the genes encoding the hormones insulin and proopiomelanocortin is potentiated by lineage-specific homeodomain proteins. The stabilization of binding of the widely expressed transcription factor Sp1 to the secretin promoter by NeuroD represents a distinct mechanism from other NeuroD target genes for increasing NeuroD-dependent transcription.

* Corresponding author. Mailing address: University of Massachusetts Medical School, Department of Medicine, Division of Gastroenterology, 364 Plantation Street LRB217, Worcester, MA 01605. Phone: (508) 856-8101. Fax: (508) 856-4770. E-mail: andrew.leiter{at}umassmed.edu

{triangledown} Published ahead of print on 17 September 2007.

Molecular and Cellular Biology, November 2007, p. 7839-7847, Vol. 27, No. 22
0270-7306/07/$08.00+0     doi:10.1128/MCB.00438-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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