Abstract
Inducible gene expression underlies the epigenetically inherited differentiation program of most immune cells. We report that the promoter of the FOXP3 gene possesses two distinct functional states: an "off state" mediated by the polycomb histone methyltransferase complex and a histone acetyltransferase-dependent "on state." Regulating these states is the presence of a Kruppel-like factor (KLF)-containing Polycomb response element. In the KLF10-/- mouse, the FOXP3 promoter is epigenetically silenced by EZH2 (Enhancer of Zeste 2)-mediated trimethylation of Histone 3 K27; thus, impaired FOXP3 induction and inappropriate adaptive T regulatory cell differentiation results in vitro and in vivo. The epigenetic transmittance of adaptive T regulatory cell deficiency is demonstrated throughout more than 40 generations of mice. These results provide insight into chromatin remodeling events key to phenotypic features of distinct T cell populations.
Original language | English (US) |
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Pages (from-to) | 34372-34385 |
Number of pages | 14 |
Journal | Journal of Biological Chemistry |
Volume | 287 |
Issue number | 41 |
DOIs | |
State | Published - Oct 5 2012 |
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology