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

doi:10.1016/j.febslet.2009.08.041

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

Medical Sciences

Research output: Contribution to journal › Article › peer-review

9 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 language	English
Pages (from-to)	3181-3186
Number of pages	6
Journal	FEBS Letters
Volume	583
Issue number	19
DOIs	https://doi.org/10.1016/j.febslet.2009.08.041
Publication status	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.febslet.2009.08.041

Cite this

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

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.",

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author = "Ferguson, {Laura A.} and Docherty, {Hilary M.} and MacKenzie, {Amanda E.} and Kevin Docherty",

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AU - Ferguson, Laura A.

AU - Docherty, Hilary M.

AU - MacKenzie, Amanda E.

AU - Docherty, Kevin

PY - 2009/10/6

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AB - 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.

KW - cell line

KW - epigenesis, genetic

KW - gene expression

KW - humans

KW - insulin

KW - insulin-like growth factor II

KW - minisatellite repeats

KW - protein engineering

KW - proteins

KW - transcription initiation site

KW - zinc fingers

KW - diabetes mellitus

KW - chromatin

KW - ZFP

KW - islets of langerhans

KW - pancreatic beta-cell

KW - Pdx1

U2 - 10.1016/j.febslet.2009.08.041

DO - 10.1016/j.febslet.2009.08.041

M3 - Article

C2 - 19733567

SN - 0014-5793

VL - 583

SP - 3181

EP - 3186

JO - FEBS Letters

JF - FEBS Letters

IS - 19

ER -

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

Abstract

Keywords

UN SDGs

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