A 3' enhancer in the IL-4 gene regulates cytokine production by Th2 cells and mast cells.
Solymar DC, Agarwal S, Bassing CH, Alt FW, Rao A.
The Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Differentiation of naive T cells into mature Th2 cells is associated with the appearance of a complex pattern of DNase I hypersensitive (DH) sites within the IL-4/IL-13 cytokine gene cluster. We show here that targeted deletion of an inducible DH site, V(A), and the adjacent conserved DH site V (CNS-2) selectively compromises IL-4 gene transcription by differentiated Th2 cells and mast cells. In mast cells, the deletion abrogates IL-4 mRNA induction, an effect mimicked by deletion of the transcription factor NFAT1 (NFATc2), which binds DH site V(A). In T cells, the deletion impairs a process of response maturation, defined by progressive increases in IL-4 levels as Th2 differentiation proceeds. These results identify an essential enhancer which regulates IL-4 gene expression in two important cell lineages in vivo.
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PMID: 12150890 [PubMed - indexed for MEDLINE]