Chromatin remodeling by the SWI/SNF-like BAF complex and STAT4 activation synergistically induce IL-12Rbeta2 expression during human Th1 cell differentiation

Autor: Elisabetta Bianchi, Sona Gasparian, Lars Rogge, Nadia Passini, Fabrice A. Letimier
Přispěvatelé: Immunorégulation, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Bioxell SpA, Bioxell, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2007
Předmět:
CD4-Positive T-Lymphocytes
Chromatin Immunoprecipitation
Chromosomal Proteins
Non-Histone
Cellular differentiation
GATA3 Transcription Factor
Biology
Models
Biological
General Biochemistry
Genetics and Molecular Biology
Chromatin remodeling
Article
03 medical and health sciences
Interferon-gamma
0302 clinical medicine
Humans
Enhancer
Promoter Regions
Genetic
Molecular Biology
Transcription factor
030304 developmental biology
Regulation of gene expression
0303 health sciences
General Immunology and Microbiology
General Neuroscience
Receptors
Interleukin-12
Interferon-alpha
Cell Differentiation
STAT4 Transcription Factor
Th1 Cells
Molecular biology
Interleukin-12
SWI/SNF
Chromatin
Gene Expression Regulation
[SDV.IMM]Life Sciences [q-bio]/Immunology
RNA Interference
Interleukin-4
Chromatin immunoprecipitation
030215 immunology
Protein Binding
Signal Transduction
Transcription Factors
Zdroj: EMBO Journal
EMBO Journal, EMBO Press, 2007, 26 (5), pp.1292-1302. ⟨10.1038/sj.emboj.7601586⟩
EMBO Journal, 2007, 26 (5), pp.1292-1302. ⟨10.1038/sj.emboj.7601586⟩
ISSN: 0261-4189
1460-2075
DOI: 10.1038/sj.emboj.7601586⟩
Popis: Interleukin-12 (IL-12) is a key cytokine for the development of T helper type 1 (Th1) responses; however, naive CD4(+) T cells do not express IL-12Rbeta2, and are therefore unresponsive to IL-12. We have examined the mechanisms that control Th1-specific expression of the human IL-12Rbeta2 gene at early time points after T-cell stimulation. We have identified a Th1-specific enhancer element that binds signal transducer and activator of transcription 4 (STAT4) in vivo in developing Th1 but not Th2 cells. T-cell receptor (TCR) signaling induced histone hyperacetylation and recruitment of BRG1, the ATPase subunit of the SWI/SNF-like BAF chromatin remodeling complex, to the IL-12Rbeta2 regulatory regions and was associated with low-level gene transcription at the IL-12Rbeta2 locus. However, high-level IL-12Rbeta2 expression required TCR triggering in the presence of IL-12. Our results indicate a synergistic role of TCR-induced chromatin remodeling and cytokine-induced STAT4 activation to direct IL-12Rbeta2 expression during Th1 cell development.
Databáze: OpenAIRE
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