Open AccessInsulin gene expression in nonexpressing cells appears to be regulated by multiple distinct negative-acting control elements.
Author(s) -
S R Cordle,
J Whelan,
Eva Henderson,
H Masuoka,
P A Weil,
Roland Stein
Publication year - 1991
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.11.5.2881
Subject(s) - enhancer , biology , transcription (linguistics) , transcription factor , negative regulatory element , enhancer rnas , gene expression , gene , response element , insulin , derepression , microbiology and biotechnology , regulatory sequence , promoter , genetics , endocrinology , linguistics , philosophy , psychological repression
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.