Transcriptional regulation by Foxp3 is associated with direct promoter occupancy and modulation of histone acetylation.

Transcriptional regulation by Foxp3 is associated with direct promoter occupancy and modulation of histone acetylation. Research Abstract Details 

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Transcriptional regulation by Foxp3 is associated with direct promoter occupancy and modulation of histone acetylation. Abstract Text:

Chunxia Chen,Emily A Rowell,Rajan M Thomas,Wayne W Hancock,Andrew D Wells,

Regulatory T cells (T(reg)) express Foxp3, a forkhead family member that is necessary and sufficient for T(reg) lineage choice and function. Ectopic expression of Foxp3 in non-T(reg) leads to repression of the interleukin 2 (IL-2) and interferon gamma (IFNgamma) genes, gain of suppressor function, and induction of genes such as CD25, GITR, and CTLA-4, but the mode by which Foxp3 enforces this program is unclear. Using chromatin immunoprecipitation, we have demonstrated that Foxp3 binds to the endogenous IL-2 and IFNgamma loci in T cells, but only after T cell receptor stimulation. This activation-induced Foxp3 binding was abrogated by cyclosporin A, suggesting a role for the phosphatase calcineurin in Foxp3 function. We have also shown that binding of Foxp3 to the IL-2 and IFNgamma genes induces active deacetylation of histone H3, a process that inhibits chromatin remodeling and opposes gene transcription. Conversely, binding of Foxp3 to the GITR, CD25, and CTLA-4 genes results in increased histone acetylation. These data indicate that Foxp3 may regulate transcription through direct chromatin remodeling and show that Foxp3 function is influenced by signals from the TCR.

Transcriptional regulation by Foxp3 is associated with direct promoter occupancy and modulation of histone acetylation. Publishing Authors By Initials

C Chen,EA Rowell,RM Thomas,WW Hancock,AD Wells,

For similar genetic processes: gene expression: transcription, genetic research abstracts see: genetic processes: gene expression: transcription, genetic research

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Transcriptional regulation by Foxp3 is associated with direct promoter occupancy and modulation of histone acetylation. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of biological chemistry

VOLUME: 281

Page Numbers: 36828-34

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 6

MONTH: 10

YEAR: 2006

Transcriptional regulation by Foxp3 is associated with direct promoter occupancy and modulation of histone acetylation. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

Transcriptional regulation by Foxp3 is associated with direct promoter occupancy and modulation of histone acetylation. Keywords Mesh Terms:

KEYWORDS: Transcription, Genetic

MESH TERMS: metabolism

Chemical & Substance for Abstract: Transcriptional regulation by Foxp3 is associated with direct promoter occupancy and modulation of histone acetylation. Information

Substance Name: Interferon Type II

Registry Number: 82115-62-6

Grant and Affiliation Information for Transcriptional regulation by Foxp3 is associated with direct promoter occupancy and modulation of histone acetylation.

AFFILIATION: Joseph Stokes, Jr. Research Institute, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.

Country: United States

AGENCY: United States NIAID

GRANT: AI059881

ACRONYM: AI

MEDLINETA: J Biol Chem

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