Department of Medicine
Animals; Base Sequence; Basic Helix-Loop-Helix Transcription Factors; Binding Sites; Cell Line; *Enhancer Elements (Genetics); *Gene Expression Regulation; Humans; Macromolecular Substances; Mice; Molecular Sequence Data; Promoter Regions (Genetics); Rats; Recombinant Fusion Proteins; Secretin; Sequence Alignment; Sp1 Transcription Factor; TCF Transcription Factors; Transcription, Genetic
Life Sciences | Medicine and Health Sciences
The basic helix-loop-helix transcription factor NeuroD1 is required for late events in neuronal differentiation, for maturation of pancreatic beta 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.
DOI of Published Version
Mol Cell Biol. 2007 Nov;27(22):7839-47. Epub 2007 Sep 17. Link to article on publisher's site
Molecular and cellular biology
Ray S, Leiter AB. (2007). The basic helix-loop-helix transcription factor NeuroD1 facilitates interaction of Sp1 with the secretin gene enhancer. Open Access Publications by UMMS Authors. https://doi.org/10.1128/MCB.00438-07. Retrieved from https://escholarship.umassmed.edu/oapubs/1331