DNA methylation changes at human Th2 cytokine genes coincide with DNase I hypersensitive site formation during CD4(+) T cell differentiation
- PMID: 12165514
- DOI: 10.4049/jimmunol.169.4.1893
DNA methylation changes at human Th2 cytokine genes coincide with DNase I hypersensitive site formation during CD4(+) T cell differentiation
Abstract
The differentiation of naive CD4(+) T lymphocytes into Th1 and Th2 lineages generates either cellular or humoral immune responses. Th2 cells express the cytokines IL-4, -5, and -13, which are implicated in asthma and atopy. Much has been published about the regulation of murine Th2 cytokine expression, but studies in human primary T cells are less common. We have developed a method for differentiating human CD45RA(+) (naive) T cells into Th1 and Th2 populations that display distinct cytokine expression profiles. We examined both CpG methylation, using bisulfite DNA modification and sequencing, and chromatin structure around the IL-4 and IL-13 genes before and after human T cell differentiation and in normal human skin fibroblasts. In naive cells, the DNA was predominantly methylated. After Th2 differentiation, DNase I hypersensitive sites (DHS) appeared at IL-4 and IL-13 and CpG demethylation occurred only around the Th2-specific DHS. Both DHS and CpG demethylation coincided with consensus binding sites for the Th2-specific transcription factor GATA-3. Although fibroblasts, like naive and Th1 cells, did not express IL-4 or IL-13, DHS and unmethylated CpG sites that were distinct from the Th2-specific sites were observed, suggesting that chromatin structure in this cluster not only varies in T cells according to IL-4/IL-13 expression but is also tissue specific.
Similar articles
-
The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells.Cell. 1997 May 16;89(4):587-96. doi: 10.1016/s0092-8674(00)80240-8. Cell. 1997. PMID: 9160750
-
Molecular analysis of a locus control region in the T helper 2 cytokine gene cluster: a target for STAT6 but not GATA3.Proc Natl Acad Sci U S A. 2004 Nov 9;101(45):16010-5. doi: 10.1073/pnas.0407031101. Epub 2004 Oct 26. Proc Natl Acad Sci U S A. 2004. PMID: 15507491 Free PMC article.
-
Cytokine transcriptional events during helper T cell subset differentiation.J Exp Med. 1996 Aug 1;184(2):397-406. doi: 10.1084/jem.184.2.397. J Exp Med. 1996. PMID: 8760793 Free PMC article.
-
Chromatin remodeling and T helper subset differentiation.IUBMB Life. 2000 Jun;49(6):473-8. doi: 10.1080/15216540050166990. IUBMB Life. 2000. PMID: 11032239 Review.
-
The function role of GATA-3 in Th1 and Th2 differentiation.Immunol Res. 2003;28(1):25-37. doi: 10.1385/IR:28:1:25. Immunol Res. 2003. PMID: 12947222 Review.
Cited by
-
DNA methylation and childhood asthma in the inner city.J Allergy Clin Immunol. 2015 Jul;136(1):69-80. doi: 10.1016/j.jaci.2015.01.025. Epub 2015 Mar 11. J Allergy Clin Immunol. 2015. PMID: 25769910 Free PMC article.
-
Transcription factor YY1 is essential for regulation of the Th2 cytokine locus and for Th2 cell differentiation.Proc Natl Acad Sci U S A. 2013 Jan 2;110(1):276-81. doi: 10.1073/pnas.1214682110. Epub 2012 Dec 17. Proc Natl Acad Sci U S A. 2013. PMID: 23248301 Free PMC article.
-
Transcriptional and epigenetic regulation of the integrin collagen receptor locus ITGA1-PELO-ITGA2.Biochim Biophys Acta. 2007 Sep-Oct;1769(9-10):546-58. doi: 10.1016/j.bbaexp.2007.06.004. Epub 2007 Jul 6. Biochim Biophys Acta. 2007. PMID: 17669516 Free PMC article.
-
Cell type-specific DNA methylation at intragenic CpG islands in the immune system.Genome Res. 2011 Jul;21(7):1074-86. doi: 10.1101/gr.118703.110. Epub 2011 May 31. Genome Res. 2011. PMID: 21628449 Free PMC article.
-
The Nasal Methylome: A Key to Understanding Allergic Asthma.Am J Respir Crit Care Med. 2017 Mar 15;195(6):829-831. doi: 10.1164/rccm.201608-1558LE. Am J Respir Crit Care Med. 2017. PMID: 28294656 Free PMC article. No abstract available.
Publication types
MeSH terms
Substances
Associated data
- Actions
- Actions
- Actions
- Actions
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Research Materials