ArticleProceedings of the National Academy of Sciences of the United States of America2013
Hypersensitive site 6 of the Th2 locus control region is essential for Th2 cytokine expression.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 38 citations in OpenAlex.
- Remodeling of Il4-Il13-Il5 locus underlies selective gene expression.Nature immunology · 2024Article
- Regulation of T helper cell differentiation by the interplay between histone modification and chromatin interaction.Immunity · 2024Article
- Molecular Mechanisms of T Helper Cell Differentiation and Functional Specialization.Immune network · 2023Review
- A Long Noncoding RNA "lnc"ed to Asthma Genetics.American journal of respiratory cell and molecular biology · 2022Article
- SATB1-mediated chromatin landscape in T cells.Nucleus (Austin, Tex.) · 2020Review
- Regulation of IgE by T follicular helper cells.Journal of leukocyte biology · 2020Review
- Identification of a T follicular helper cell subset that drives anaphylactic IgE.Science (New York, N.Y.) · 2019Article
- A conserved enhancer regulates Il9 expression in multiple lineages.Nature communications · 2018Article
- The Th2 gene cluster unraveled: role of RHS6.Allergy · 2017Article
- Article
- BATF Modulates the Th2 Locus Control Region and Regulates CD4+ T Cell Fate during Antihelminth Immunity.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Article
- Review
- Review
- [Genetics of atopic eczema. An update].Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete · 2015Article
- Oct-1 regulates IL-17 expression by directing interchromosomal associations in conjunction with CTCF in T cells.Molecular cell · 2014Article
- Transcriptional regulation of T helper type 2 differentiation.Immunology · 2014Review
- Epigenetic regulation of asthma and allergic disease.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2014Review
- 'All things considered': transcriptional regulation of T helper type 2 cell differentiation from precursor to effector activation.Immunology · 2013Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
Abstract
The T helper type 2 (Th2) cytokine genes Il4, Il5, and Il13 are contained within a 140-kb region of mouse chromosome 11 and their expression is controlled by a locus control region (LCR) embedded within this locus. The LCR is composed of a number of DNase I-hypersensitive sites (HSs), which are believed to encompass the regulatory core of the LCR. To determine the function of these sites, mutant mice were generated in which combinations of these HSs had been deleted from the endogenous LCR, and the effect on Th2 cytokine expression was assessed through the use of in vivo and in vitro models. These experiments revealed that, although all of the hypersensitive sites analyzed are important for appropriate LCR function, some sites are more important than others in regulating cytokine expression. Interestingly, each LCR mutation showed contrasting effects on cytokine expression, in some cases with mutants displaying opposing phenotypes between in vitro cultures and in vivo immunizations. These studies indicated that Rad50 hypersensitive site 6 was the singularly most important HS for Th2 cytokine expression, displaying consistent reductions in cytokine levels in all models tested. Furthermore analysis of chromatin modifications revealed that deletion of Rad50 hypersensitive site 6 impacted epigenetic modifications at the promoters of the Il4, Il5, and Il13 genes as well as other regulatory sites within the Th2 locus.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.