The single nucleotide variant rs12722489 determines differential estrogen receptor binding and enhancer properties of an IL2RA intronic region

We studied functional effect of rs12722489 single nucleotide polymorphism located in the first intron of human IL2RA gene on transcriptional regulation. This polymorphism is associated with multiple autoimmune conditions (rheumatoid arthritis, multiple sclerosis, Crohn's disease, and ulcerative...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2017-02, Vol.12 (2), p.e0172681-e0172681
Main Authors: Afanasyeva, Marina A, Putlyaeva, Lidia V, Demin, Denis E, Kulakovskiy, Ivan V, Vorontsov, Ilya E, Fridman, Marina V, Makeev, Vsevolod J, Kuprash, Dmitry V, Schwartz, Anton M
Format: Article
Language:English
Subjects:
Affinity
Alleles
Arthritis
Assaying
Autoimmune diseases
Base Sequence
Binding Sites
Biology and Life Sciences
Cell Line, Transformed
Chromatin
Chromatin Immunoprecipitation
Crohn's disease
Crohns disease
Cytokines
Dendritic cells
Deoxyribonucleic acid
DNA
Electrophoretic mobility
Electrophoretic Mobility Shift Assay
Endocrinology
Epigenetics
Estrogen Receptor alpha - genetics
Estrogen Receptor alpha - metabolism
Estrogen receptors
Estrogens
Gene expression
Gene Expression Regulation
Gene polymorphism
Gene regulation
Genes, Reporter
Genetic aspects
Genetics
Genomes
Human T-lymphotropic virus 1 - genetics
Humans
Immunology
Immunoprecipitation
Interleukin 2 receptors
Interleukin-2 Receptor alpha Subunit - genetics
Interleukin-2 Receptor alpha Subunit - metabolism
Introns
Leukemia
Localization
Luciferases - genetics
Luciferases - metabolism
Lymphocytes T
Medicine and Health Sciences
Molecular biology
Multiple sclerosis
Phenotypes
Physical Sciences
Physics
Polymorphism
Polymorphism, Single Nucleotide
Protein Binding
Research and Analysis Methods
Response Elements
Retroviridae
Rheumatoid arthritis
Science
Single nucleotide polymorphisms
Single-nucleotide polymorphism
T-Lymphocytes, Regulatory - cytology
T-Lymphocytes, Regulatory - metabolism
Transcription
Transcription factors
Ulcerative colitis
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:We studied functional effect of rs12722489 single nucleotide polymorphism located in the first intron of human IL2RA gene on transcriptional regulation. This polymorphism is associated with multiple autoimmune conditions (rheumatoid arthritis, multiple sclerosis, Crohn's disease, and ulcerative colitis). Analysis in silico suggested significant difference in the affinity of estrogen receptor (ER) binding site between alternative allelic variants, with stronger predicted affinity for the risk (G) allele. Electrophoretic mobility shift assay showed that purified human ERα bound only G variant of a 32-bp genomic sequence containing rs12722489. Chromatin immunoprecipitation demonstrated that endogenous human ERα interacted with rs12722489 genomic region in vivo and DNA pull-down assay confirmed differential allelic binding of amplified 189-bp genomic fragments containing rs12722489 with endogenous human ERα. In a luciferase reporter assay, a kilobase-long genomic segment containing G but not A allele of rs12722489 demonstrated enhancer properties in MT-2 cell line, an HTLV-1 transformed human cell line with a regulatory T cell phenotype.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0172681