CMS physics technical design report : Addendum on high density QCD with heavy ions

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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 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

Endogenous ERα binds genomic region containing rs12722489 and binding efficiency depends on the allelic variant.

<p>(A) Chromatin immunoprecipitation was performed in Jurkat and MT-2 cells using antibodies to human ERα. Precipitated DNA was analyzed by real-time PCR using primers specific to a 189-bp genomic sequence containing rs12722489. *<i>p<0</i>.<i>05</i> comparing to isotype control. **<i>p<0</i>.<i>05</i> comparing to Jurkat cells. (B) DNA pull-down assay was performed using MT-2 nuclear extract, 189-bp amplicons from human <i>IL2RA</i> gene containing rs12722489 allelic variants, and antibodies to human ERα. *<i>p<0</i>.<i>05</i> comparing to isotype control. **<i>p<0</i>.<i>05</i> comparing to the G variant. Data from at least 3 independent experiments are represented as mean±SEM.</p

Epigenetic marks located at rs12722489 and rs706779 according to the Roadmap Epigenomics Consortium data [25].

<p>Epigenetic marks located at rs12722489 and rs706779 according to the Roadmap Epigenomics Consortium data [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0172681#pone.0172681.ref025" target="_blank">25</a>].</p

SNPs of the <i>IL2RA</i> locus significantly associated with two or more autoimmune diseases according to GRASP database [21].

<p>SNPs of the <i>IL2RA</i> locus significantly associated with two or more autoimmune diseases according to GRASP database [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0172681#pone.0172681.ref021" target="_blank">21</a>].</p

Electroweak parameters of the z0 resonance and the standard model

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