An engineered zinc finger protein reveals a role for the insulin VNTR in the regulation of the insulin and adjacent IGF2 genes

Laura A. Ferguson, Hilary M. Docherty, Amanda E. MacKenzie, Kevin Docherty

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

An engineered zinc finger protein (eZFP) was isolated from a library based on its ability to activate expression of the endogenous insulin gene in HEK-293 cells. Using a panel of insulin promoter constructs, the eZFP was shown to act through the variable number of tandem repeat (VNTR) region located 365 base pairs upstream of the transcription start site. The eZFP also activated expression of the IGF2 gene that lies close to INS on chromosome 11p15. These results demonstrate that the INSVNTR controls expression of the insulin and IGF2 genes and provide a mechanistic explanation for previous studies that demonstrated an association between INSVNTR genotypes and placental levels of IGF2.
Original languageEnglish
Pages (from-to)3181-3186
Number of pages6
JournalFEBS Letters
Volume583
Issue number19
DOIs
Publication statusPublished - 6 Oct 2009

Keywords

  • cell line
  • epigenesis, genetic
  • gene expression
  • humans
  • insulin
  • insulin-like growth factor II
  • minisatellite repeats
  • protein engineering
  • proteins
  • transcription initiation site
  • zinc fingers
  • diabetes mellitus
  • chromatin
  • ZFP
  • islets of langerhans
  • pancreatic beta-cell
  • Pdx1

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