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Transcriptional Control of the TNF Gene

Open access
Falvo, James V., Tsytsykova, Alla V., Goldfeld, Anne E.·2010·Current Directions in Autoimmunity

Abstract

The cytokine TNF is a critical mediator of immune and inflammatory responses. The TNF gene is an immediate early gene, rapidly transcribed in a variety of cell types following exposure to a broad range of pathogens and signals of inflammation and stress. Regulation of TNF gene expression at the transcriptional level is cell type- and stimulus-specific, involving the recruitment of distinct sets of transcription factors to a compact and modular promoter region. In this review, we describe our current understanding of the mechanisms through which TNF transcription is specifically activated by a variety of extracellular stimuli in multiple cell types, including T cells, B cells, macrophages, mast cells, dendritic cells, and fibroblasts. We discuss the role of nuclear factor of activated T cells and other transcription factors and coactivators in enhanceosome formation, as well as the contradictory evidence for a role for nuclear factor kappaB as a classical activator of the TNF gene. We describe the impact of evolutionarily conserved cis-regulatory DNA motifs in the TNF locus upon TNF gene transcription, in contrast to the neutral effect of single nucleotide polymorphisms. We also assess the regulatory role of chromatin organization, epigenetic modifications, and long-range chromosomal interactions at the TNF locus.

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Metadata

Authors
Falvo, J. V., Tsytsykova, A. V., & Goldfeld, A. E.
Venue
Current Directions in Autoimmunity
Publisher
KARGER
Published
2010
Volume
11
Pages
27-60
ISSN
1422-2132 (ISSN-L)
OpenAlex
W1550772045
Cited by
281
References
13
FWCI
15.53
Type
book chapter
Language
en
Open access
green

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CoChat. (2026). Citation check: Transcriptional Control of the TNF Gene. https://app.cochat.ai/papers/10.1159/000289196
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Falvo, J. V., Tsytsykova, A. V., & Goldfeld, A. E. (2010). Transcriptional Control of the TNF Gene. Current Directions in Autoimmunity. https://doi.org/10.1159/000289196

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