Journal
BLOOD
Volume 116, Issue 9, Pages 1443-1453Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2009-11-252205
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Funding
- Academy of Finland
- National Technology Agency
- Sigrid Juselius Foundation
- Turku University Hospital
- Finnish Cultural Foundation
- Ida Montin Foundation
- Vaino and Laina Kivi Foundation
- European Commission [EC-FP7-SYBILLA-201106, EC-FP7-NANOMMUNE-214281, EC-FP7-DIABIMMUNE-202063]
- Department of Biotechnology, Government of India
- Wellcome Trust, United Kingdom
- University grants commission, India
- Council of Scientific and Industrial Research, India
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Special AT-rich binding protein 1 (SATB1) is a global chromatin organizer and a transcription factor regulated by interleukin-4 (IL-4) during the early T helper 2 (Th2) cell differentiation. Here we show that SATB1 controls multiple IL-4 target genes involved in human Th cell polarization or function. Among the genes regulated by SATB1 is that encoding the cytokine IL-5, which is predominantly produced by Th2 cells and plays a key role in the development of eosinophilia in asthma. We demonstrate that, during the early Th2 cell differentiation, IL-5 expression is repressed through direct binding of SATB1 to the IL-5 promoter. Furthermore, SATB1 knockdown-induced upregulation of IL-5 is partly counteracted by down-regulating GATA3 expression using RNAi in polarizing Th2 cells. Our results suggest that a competitive mechanism involving SATB1 and GATA3 regulates IL-5 transcription, and provide new mechanistic insights into the stringent regulation of IL-5 expression during human Th2 cell differentiation. (Blood. 2010;116(9):1443-1453)
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