Insulin gene expression in nonexpressing cells appears to be regulated by multiple distinct negative-acting control elements.
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.
Cordle
S R
SR
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee 37232.
Whelan
J
J
Henderson
E
E
Masuoka
H
H
Weil
P A
PA
Stein
R
R
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002872:Chromosome Deletion; D004268:DNA-Binding Proteins / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D005796:Genes; D006367:HeLa Cells / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000235:genetics*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D015345:Oligonucleotide Probes; D051381:Rats; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D007328:Insulin; D015345:Oligonucleotide Probes