Chromatin-based regulation of cytokine transcription in Th2 cells and mast cells
Open Access
- 30 September 2005
- journal article
- research article
- Published by Oxford University Press (OUP) in International Immunology
- Vol. 17 (11), 1513-1524
- https://doi.org/10.1093/intimm/dxh329
Abstract
Th2 cells and mast cells are major sources of IL4, IL5 and IL13, cytokines that mediate immunity against parasites and are also central players in the pathophysiology of asthma, allergy and atopic disease. We asked whether Th2 cells and mast cells, which belong to the lymphoid and myeloid lineages, respectively, use different cis-acting regulatory regions to transcribe the cytokine genes. Comparison of DNase I hypersensitivity patterns at the RAD50/IL4/IL13 locus revealed that most hypersensitive sites (HSs) are common to Th2 and mast cells, but two regions [conserved non-coding sequence (CNS) 1 and mast cell HSs] show cell type-specific differences. CNS-1, one of the most highly conserved CNS regions in the RAD50/IL13/IL4 locus, displays two strong DNase I HSs in Th2 cells but is not DNase I hypersensitive in mast cells, explaining a previous finding that deletion of CNS-1 impairs cytokine expression in Th2 cells but not in mast cells. Conversely, two constitutive HSs (mast cell HSs) in the first intron of the IL13 gene are present in mast cells but not in Th2 cells; these sites develop early during mast cell differentiation and may have a role in maintaining accessibility of the IL13 locus to high-level transcription in stimulated cells.Keywords
This publication has 43 references indexed in Scilit:
- Th2-Specific Chromatin Remodeling and Enhancer Activity in the Th2 Cytokine Locus Control RegionImmunity, 2004
- Bioinformatics for the 'bench biologist': how to find regulatory regions in genomic DNANature Immunology, 2004
- Role of NFAT Proteins in IL13 Gene Transcription in Mast CellsPublished by Elsevier BV ,2004
- Identification of a Conserved GATA3 Response Element Upstream Proximal from the Interleukin-13 Gene LocusJournal of Biological Chemistry, 2002
- TH cell differentiation is accompanied by dynamic changes in histone acetylation of cytokine genesNature Immunology, 2002
- The Proto-Oncogene c-maf Is Responsible for Tissue-Specific Expression of Interleukin-4Cell, 1996
- Essential role of Stat6 in IL-4 signallingNature, 1996
- Stat6 Is Required for Mediating Responses to IL-4 and for the Development of Th2 CellsImmunity, 1996
- NUCLEASE HYPERSENSITIVE SITES IN CHROMATINAnnual Review of Biochemistry, 1988
- Neoplastic transformation of mast cells by Abelson-MuLV: abrogation of IL-3 dependence by a nonautocrine mechanismCell, 1985