Polycomb antagonizes p300/CREB-binding protein-associated factor to silence FOXP3 in a Kruppel-like factor-dependent manner. J Biol Chem 2012 Oct 05;287(41):34372-85
Date
08/17/2012Pubmed ID
22896699Pubmed Central ID
PMC3464543DOI
10.1074/jbc.M111.325332Scopus ID
2-s2.0-84867266681 (requires institutional sign-in at Scopus site) 53 CitationsAbstract
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.
Author List
Xiong Y, Khanna S, Grzenda AL, Sarmento OF, Svingen PA, Lomberk GA, Urrutia RA, Faubion WA JrAuthors
Gwen Lomberk PhD Professor in the Surgery department at Medical College of WisconsinRaul A. Urrutia MD Center Director, Professor in the Surgery department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsChromatin Assembly and Disassembly
Early Growth Response Transcription Factors
Enhancer of Zeste Homolog 2 Protein
Forkhead Transcription Factors
Gene Silencing
Kruppel-Like Transcription Factors
Male
Mice
Mice, Knockout
Polycomb Repressive Complex 2
Polycomb-Group Proteins
Response Elements
T-Lymphocytes, Regulatory
p300-CBP Transcription Factors
