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PMID: 19818655 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

CCCTC-binding factor and the transcription factor T-bet orchestrate T helper 1 cell-specific structure and function at the interferon-gamma locus.

Immunity ·Vol. 31 ·No. 4 ·2009-10-16 ·Pages 551-64

Sekimata M, Pérez-Melgosa M, Miller SA, Weinmann AS, Sabo PJ, Sandstrom R, Dorschner MO, Stamatoyannopoulos JA, Wilson CB

Abstract

How cell type-specific differences in chromatin conformation are achieved and their contribution to gene expression are incompletely understood. Here we identify a cryptic upstream orchestrator of interferon-gamma (IFNG) transcription, which is embedded within the human IL26 gene, compromised of a single CCCTC-binding factor (CTCF) binding site and retained in all mammals, even surviving near-complete evolutionary deletion of the equivalent gene encoding IL-26 in rodents. CTCF and cohesins occupy this element in vivo in a cell type-nonspecific manner. This element is juxtaposed to two other sites located within the first intron and downstream of Ifng, where CTCF, cohesins, and the transcription factor T-bet bind in a T helper 1 (Th1) cell-specific manner. These interactions, close proximity of other elements within the locus to each other and to the gene encoding interferon-gamma, and robust murine Ifng expression are dependent on CTCF and T-bet. The results demonstrate that cooperation between architectural (CTCF) and transcriptional enhancing (T-bet) factors and the elements to which they bind is required for proper Th1 cell-specific expression of Ifng.

MeSH Terms
Animals CCCTC-Binding Factor CD4-Positive T-Lymphocytes/immunology,metabolism Cell Cycle Proteins/genetics,immunology,metabolism Cells, Cultured Chromatin/immunology,metabolism Chromosomal Proteins, Non-Histone/genetics,immunology,metabolism Humans Interferon-gamma/genetics,immunology,metabolism Interleukins/genetics,immunology,metabolism Introns/genetics,immunology Mice Mice, Inbred C57BL Mice, Transgenic Rats Repressor Proteins/genetics,immunology,metabolism T-Box Domain Proteins/genetics,immunology,metabolism Th1 Cells/immunology,metabolism
Chemicals
CCCTC-Binding Factor CTCF protein, human Cell Cycle Proteins Chromatin Chromosomal Proteins, Non-Histone Ctcf protein, mouse IL26 protein, human Interleukins Repressor Proteins T-Box Domain Proteins T-box transcription factor TBX21 cohesins Interferon-gamma
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Sekimata Masayuki
Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195, USA.
Pérez-Melgosa Mercedes
Miller Sara A
Weinmann Amy S
Sabo Peter J
Sandstrom Richard
Dorschner Michael O
Stamatoyannopoulos John A
Wilson Christopher B
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2009.08.021
Published
2009-10-16
Epub
2009-00-08
Pages
551-64
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC2810421
Subset
IM
Grants
NIGMS NIH HHS · R01 GM071923 · United States
NIAID NIH HHS · R01 AI071272-08 · United States
NHGRI NIH HHS · U54 HG004592-03S1 · United States
NIAID NIH HHS · N01AI40069 · United States
PHS HHS · GMT3207270 · United States
NHGRI NIH HHS · U54 HG004592-02S1 · United States
NIGMS NIH HHS · R01 GM071852 · United States
NIAID NIH HHS · R01 AI061061-05 · United States
NIGMS NIH HHS · R01 GM071923-04 · United States
NICHD NIH HHS · R01 HD018184-28 · United States
NIGMS NIH HHS · R01 GM071852-05 · United States
NIAID NIH HHS · R01-AI071282 · United States
NIGMS NIH HHS · R01-GM71923 · United States
NIAID NIH HHS · N01 AI040069 · United States
NIAID NIH HHS · R01-AI061061 · United States
NIGMS NIH HHS · R01-GM71852 · United States
NHGRI NIH HHS · U54 HG004592-02 · United States
NHGRI NIH HHS · U54 HG004592-03 · United States
NHGRI NIH HHS · U54-HG004592 · United States
NIGMS NIH HHS · R01 GM071923-03 · United States
NIGMS NIH HHS · R01 GM071852-04 · United States
NICHD NIH HHS · R01 HD018184-29 · United States
NIAID NIH HHS · R01 AI061061 · United States
NICHD NIH HHS · R01 HD018184 · United States
NICHD NIH HHS · R01-HD18184 · United States
NIAID NIH HHS · R01 AI071272-07 · United States
NHGRI NIH HHS · U54 HG004592 · United States
External Links
PubMed source DOI: 10.1016/j.immuni.2009.08.021 PMC Full Text View journal details
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