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Blood. 2010 Sep 2;116(9):1443-53. doi: 10.1182/blood-2009-11-252205. Epub 2010 Jun 3.

SATB1 dictates expression of multiple genes including IL-5 involved in human T helper cell differentiation.

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  • 1Turku Centre for Biotechnology, University of Turku and Abo Akademi University, Finland.

Abstract

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 up-regulation 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.

PMID:
20522714
PMCID:
PMC2938835
DOI:
10.1182/blood-2009-11-252205
[PubMed - indexed for MEDLINE]
Free PMC Article
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