Polycomb antagonizes p300/CREB-binding protein-associated factor to silence FOXP3 in a Kruppel-like factor-dependent manner

Yuning Xiong, Sahil Khannas, Adrienne L. Grzenda, Olga F. Sarmento, Phyllis A. Svingen, Gwen A. Lomberk, Raul A. Urrutia, William A. Faubion

Research output: Contribution to journalArticle

37 Scopus citations

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 languageEnglish (US)
Pages (from-to)34372-34385
Number of pages14
JournalJournal of Biological Chemistry
Volume287
Issue number41
DOIs
StatePublished - Oct 5 2012

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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