Insulin gene expression in nonexpressing cells appears to be regulated by multiple distinct negative-acting control elements.

Cordle SR, Whelan J, Henderson E, Masuoka H, Weil PA, Stein R
Mol Cell Biol. 1991 11 (5): 2881-6

PMID: 2017182 · PMCID: PMC360077 · DOI:10.1128/mcb.11.5.2881

Selective transcription of the insulin gene in pancreatic beta cells is regulated by its enhancer, located between nucleotides -340 and -91 relative to the transcription start site. Transcription from the enhancer is controlled by both positive- and negative-acting cellular factors. Cell-type-specific expression is mediated principally by a single cis-acting enhancer element located between -100 and -91 in the rat insulin II gene (referred to as the insulin control element [ICE]), which is acted upon by both of these cellular activities. Analysis of the effect of 5' deletions within the insulin enhancer has identified a region between nucleotides -217 and -197 that is also a site of negative control. Deletion of these sequences from the 5' end of the enhancer leads to transcription of the enhancer in non-insulin-producing cells, even though the ICE is intact. Derepression of this ICE-mediated effect was shown to be due to the binding of a ubiquitously distributed cellular factor to a sequence element which resides just upstream of the ICE (i.e., between nucleotides -110 and -100). We discuss the possible relationship of these results to cell-type-specific regulation of the insulin gene.

MeSH Terms (16)

Animals Base Sequence Cell Line Chromosome Deletion DNA-Binding Proteins Enhancer Elements, Genetic Gene Expression Regulation Genes HeLa Cells Humans Insulin Molecular Sequence Data Mutagenesis, Site-Directed Oligonucleotide Probes Rats Transcription, Genetic

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