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 Alvis Faubion

Research output: Contribution to journalArticle

33 Citations (Scopus)

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

Fingerprint

Kruppel-Like Transcription Factors
Histone Acetyltransferases
T-cells
Response Elements
Gene expression
Histones
Chromatin
Genes
Chromatin Assembly and Disassembly
Regulatory T-Lymphocytes
Epigenomics
Cell Differentiation
T-Lymphocytes
Gene Expression
Population
p300-CBP-associated factor
histone methyltransferase
In Vitro Techniques

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Polycomb antagonizes p300/CREB-binding protein-associated factor to silence FOXP3 in a Kruppel-like factor-dependent manner. / Xiong, Yuning; Khannas, Sahil; Grzenda, Adrienne L.; Sarmento, Olga F.; Svingen, Phyllis A.; Lomberk, Gwen A.; Urrutia, Raul A.; Faubion, William Alvis.

In: Journal of Biological Chemistry, Vol. 287, No. 41, 05.10.2012, p. 34372-34385.

Research output: Contribution to journalArticle

Xiong, Yuning ; Khannas, Sahil ; Grzenda, Adrienne L. ; Sarmento, Olga F. ; Svingen, Phyllis A. ; Lomberk, Gwen A. ; Urrutia, Raul A. ; Faubion, William Alvis. / Polycomb antagonizes p300/CREB-binding protein-associated factor to silence FOXP3 in a Kruppel-like factor-dependent manner. In: Journal of Biological Chemistry. 2012 ; Vol. 287, No. 41. pp. 34372-34385.
@article{de9e7acb597d458f854564bc18e645a6,
title = "Polycomb antagonizes p300/CREB-binding protein-associated factor to silence FOXP3 in a Kruppel-like factor-dependent manner",
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.",
author = "Yuning Xiong and Sahil Khannas and Grzenda, {Adrienne L.} and Sarmento, {Olga F.} and Svingen, {Phyllis A.} and Lomberk, {Gwen A.} and Urrutia, {Raul A.} and Faubion, {William Alvis}",
year = "2012",
month = "10",
day = "5",
doi = "10.1074/jbc.M111.325332",
language = "English (US)",
volume = "287",
pages = "34372--34385",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "41",

}

TY - JOUR

T1 - Polycomb antagonizes p300/CREB-binding protein-associated factor to silence FOXP3 in a Kruppel-like factor-dependent manner

AU - Xiong, Yuning

AU - Khannas, Sahil

AU - Grzenda, Adrienne L.

AU - Sarmento, Olga F.

AU - Svingen, Phyllis A.

AU - Lomberk, Gwen A.

AU - Urrutia, Raul A.

AU - Faubion, William Alvis

PY - 2012/10/5

Y1 - 2012/10/5

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84867266681&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84867266681&partnerID=8YFLogxK

U2 - 10.1074/jbc.M111.325332

DO - 10.1074/jbc.M111.325332

M3 - Article

VL - 287

SP - 34372

EP - 34385

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 41

ER -