Association of insulin-like growth factor 2 with the insulin-linked polymorphic region in cultured fetal thymus cells.
The insulin-linked polymorphic region (ILPR) is a regulatory sequence in the promoter region upstream of the human insulin gene and is widely recognized as a locus of type 1 diabetes susceptibility. Polymorphism of the ILPR sequence can affect expression of both insulin and the adjacent insulin-like growth factor 2 (IGF-2) gene. Several ILPR variants form G-quadruplex DNA structures in vitro that exhibit affinity binding to insulin and IGF-2. It has been suggested that the ILPR may form G-quadruplexes in vivo as well, raising the possibility that insulin and IGF-2 may bind to these structures in the ILPR in chromatin of live cells. This work establishes the presence of IGF-2 in the nucleus of cells cultured from human fetal thymus and its association with the ILPR in the chromatin of these cells. In vitro experiments support the involvement of G-quadruplex DNA in the binding interaction.
Wang
Yuexi
Y
Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180, USA.
Zhang
Huiping
H
Ligon
Lee A
LA
McGown
Linda B
LB
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D003920:Diabetes Mellitus / Q000235:genetics; D005333:Fetus / Q000166:cytology*; D054856:G-Quadruplexes; D005786:Gene Expression Regulation; D006801:Humans; D055767:Immobilized Proteins / Q000737:chemistry / Q000378:metabolism; D007328:Insulin / Q000235:genetics* / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D021381:Protein Transport; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D012822:Silicon Dioxide / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013499:Surface Properties; D013950:Thymus Gland / Q000166:cytology*
D002843:Chromatin; D055767:Immobilized Proteins; D007328:Insulin; D009841:Oligonucleotides; D007335:Insulin-Like Growth Factor II; D012822:Silicon Dioxide