Monocyte-specific Accessibility of a Matrix Attachment Region in the Tumor Necrosis Factor Locus

Biglione, Sebastian; Tsytsykova, Alla V.; Goldfeld, Anne E.

doi:10.1074/jbc.m111.272476

Cited by 4 publications

(12 citation statements)

References 38 publications

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“…Depending on cell type and stimulus, discrete sets of transcription factors and coactivators assemble at the proximal TNF promoter to form higher-order nucleoprotein complexes called enhanceosomes, which drive transcription of the gene (Barthel et al, 2003; Falvo, Brinkman, et al, 2000; Falvo et al, 2008; Falvo, Uglialoro, et al, 2000; Tsai et al, 2000; Tsytsykova & Goldfeld, 2002). This cell type- and stimulus-specific activation of TNF gene transcription is also a key feature of epigenetic regulation of the gene (Tsytsykova, Rajsbaum, et al, 2007, Biglione et al, 2011). …”

Section: Cytokine Gene Regulationmentioning

confidence: 99%

“…A number of constitutive and inducible DNase I hypersensitive sites (HSs), which occur within evolutionarily conserved sequences, have been detected across the TNF/LT locus in a cell type-specific fashion (Barthel & Goldfeld, 2003; Biglione et al, 2011; Ranjbar, Rajsbaum, & Goldfeld, 2006; Taylor et al, 2008; Tsytsykova, Rajsbaum, et al, 2007; Fig. 2.2A).…”

Section: Cytokine Gene Regulationmentioning

confidence: 99%

“…For example, strong HSs are present at the TNF and LTA promoters in multiple cell types. In addition, a number of these sites are enhanced in response to cellular activation, bind to distinct activators, and are cell type-specific (Barthel & Goldfeld, 2003; Biglione et al, 2011; Ranjbar et al, 2006; Tsytsykova, Rajsbaum, et al, 2007). …”

Section: Cytokine Gene Regulationmentioning

confidence: 99%

“…Epigenetic modifications have been characterized at a number of HSs across the TNF / LT locus in human and murine primary cells and cell lines (Biglione et al, 2011; Ranjbar et al, 2006; Tsytsykova et al, 2007; Fig. 2.2A).…”

Section: Cytokine Gene Regulationmentioning

confidence: 99%

“…Furthermore, in murine primary CD4 + T cells, anti-CD3/CD28 stimulation resulted in increased acetylation of histones H3 and H4 at the Tnf promoter as well as distal enhancers HSS−9 and HSS+3 (sites 9 kb upstream and 3 kb downstream of the Tnf TSS, respectively; Tsytsykova, Rajsbaum, et al, 2007). H3ac and H4ac marks are also enriched at both the Tnf promoter and a novel monocyte-specific matrix attachment region (MAR) at HSS−7 of the Tnf / Lt locus in the murine J774 monocytic cell line (Biglione et al, 2011). PHA/ PMA stimulation also results in recruitment of the HATs PCAF and Gcn5 to the TNF promoter in Jurkat cells (Ranjbar et al, 2006).…”

Section: Cytokine Gene Regulationmentioning

confidence: 99%

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Epigenetic Control of Cytokine Gene Expression

Falvo

Jasenosky

Kruidenier

et al. 2013

Advances in Immunology

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Epigenetics encompasses transient and heritable modifications to DNA and nucleosomes in the native chromatin context. For example, enzymatic addition of chemical moieties to the N-terminal “tails” of histones, particularly acetylation and methylation of lysine residues in the histone tails of H3 and H4, plays a key role in regulation of gene transcription. The modified histones, which are physically associated with gene regulatory regions that typically occur within conserved noncoding sequences, play a functional role in active, poised, or repressed gene transcription. The “histone code” defined by these modifications, along with the chromatin-binding acetylases, deacetylases, methylases, demethylases, and other enzymes that direct modifications resulting in specific patterns of histone modification, shows considerable evolutionary conservation from yeast to humans. Direct modifications at the DNA level, such as cytosine methylation at CpG motifs that represses promoter activity, are another highly conserved epigenetic mechanism of gene regulation. Furthermore, epigenetic modifications at the nucleosome or DNA level can also be coupled with higher-order intra- or interchromosomal interactions that influence the location of regulatory elements and that can place them in an environment of specific nucleoprotein complexes associated with transcription. In the mammalian immune system, epigenetic gene regulation is a crucial mechanism for a range of physiological processes, including the innate host immune response to pathogens and T cell differentiation driven by specific patterns of cytokine gene expression. Here, we will review current findings regarding epigenetic regulation of cytokine genes important in innate and/or adaptive immune responses, with a special focus upon the tumor necrosis factor/lymphotoxin locus and cytokine-driven CD4+ T cell differentiation into the Th1, Th2, and Th17 lineages.

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Section: Cytokine Gene Regulationmentioning

confidence: 99%

Section: Cytokine Gene Regulationmentioning

confidence: 99%

Section: Cytokine Gene Regulationmentioning

confidence: 99%

Section: Cytokine Gene Regulationmentioning

confidence: 99%

Section: Cytokine Gene Regulationmentioning

confidence: 99%

See 3 more Smart Citations

Epigenetic Control of Cytokine Gene Expression

Falvo

Jasenosky

Kruidenier

et al. 2013

Advances in Immunology

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Dynamic changes in chromatin conformation at theTNFtranscription start site inThelper lymphocyte subsets

et al. 2013

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Tumor necrosis factor (TNF) is one of the key primary response genes in the immuneKeywords: Chromatin conformation r Th cells r T lymphocyte r TNF r Transcription start site Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionTumor necrosis factor (TNF) is a pleiotropic cytokine expressed by various types of lymphoid and myeloid cells, including T cells, B cells, NK cells, monocytes, macrophages, DCs, and mast cells (reviewed in [1,2]). TNF is involved in development, homeostasis, and activation of the immune system [3][4][5][6][7][8]. Physiological functions mediated by TNF depend on the cellular sources and the molecular form of this cytokine [9][10][11]. In particular, TNF produced by macrophages and T cells plays different roles in immune and inflammatory reactions [9,10]. TNF is the primary response gene in macrophages where it has a permissive chromatin conformation [12,13]. Even without stimulation, the proximal TNF Correspondence: Dr. Yury V. Shebzukhov e-mail: shebzukhov@drfz.de promoter and transcription start site (TSS) have an open chromatin configuration in primary monocytes and macrophages and in the majority of tested myelomonocytic cell lines [14][15][16][17][18][19][20][21][22]. Various T-cell subsets produce different amounts of TNF in correlation with their pathophysiological potential [23]. Earlier studies [24] as well as recent advances in high-throughput analysis of DNaseI chromatin accessibility indicate that the proximal part of the TNF promoter in T cells is open (Supporting Information Fig. 1); however, in contrast to macrophages, the TSS of TNF in T cells acquires open chromatin conformation only after activation or polarization under Th1 or Th17 (where Th is T helper) conditions. TNF gene expression in T cells is regulated by the NFAT and AP-1 families of transcription factors; in particular, activation of the proximal TNF promoter region involves functional interactions with the transcription factors NFATc2 and c-Jun [25][26][27][28][29][30][31]. Numerous reports also supported the involvement of the NF-κB family members in transcriptional regulation of the TNF gene inwww.eji-journal.eu 252Yury V. Shebzukhov et al. Eur. J. Immunol. 2014. 44: 251-264 macrophages, in spite of the lack of canonical high-affinity NF-κB binding sites within the proximal TNF promoter [32][33][34][35][36][37][38][39]. However, specific role of NF-κB family members in regulation of the TNF gene is still being debated ([1, 2] and Discussion section). In murine T cells, members of the NF-κB family were shown to bind to the distal part of the TNF promoter [40] and to the enhancer element immediately downstream of the TNF gene (3 -TNF enhancer) [24], but the functional significance of these interactions is not clear.Here, we demonstrate the difference in chromatin structure around TNF TSS between T cells and macrophages. We further show that active forms of c-Jun and NFATc2 transcription factors are involved in chromatin remodeling oc...

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A Distal Locus Element Mediates IFN-γ Priming of Lipopolysaccharide-Stimulated TNF Gene Expression

2014

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SUMMARY IFN-γ priming sensitizes monocytes/macrophages to lipopolysaccharide (LPS) stimulation, resulting in augmented expression of a set of genes including TNF. Here, we demonstrate that IFN-γ priming of LPS-stimulated TNF transcription requires a distal TNF/LT locus element 8 kb upstream of the TNF transcription start site (hHS-8). IFN-γ stimulation leads to increased DNase I accessibility of hHS-8 and its recruitment of IRF1, and subsequent LPS stimulation enhances H3K27 acetylation and induces enhancer RNA synthesis at hHS-8. Ablation of IRF1 or targeting the hHS-8 IRF1 binding site in vivo with Cas9 linked to the KRAB repressive domain abolishes IFN-γ priming while LPS induction of the gene is unaffected. Thus, IFN-γ poises a distal enhancer in the TNF/LT locus by chromatin remodeling and IRF1 recruitment, which then drives enhanced TNF gene expression in response to a secondary TLR stimulus.

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Monocyte-specific Accessibility of a Matrix Attachment Region in the Tumor Necrosis Factor Locus

Cited by 4 publications

References 38 publications

Epigenetic Control of Cytokine Gene Expression

Epigenetic Control of Cytokine Gene Expression

Dynamic changes in chromatin conformation at theTNFtranscription start site inThelper lymphocyte subsets

A Distal Locus Element Mediates IFN-γ Priming of Lipopolysaccharide-Stimulated TNF Gene Expression

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