T Cell-Specific Expression of the Human TNF-α Gene Involves a Functional and Highly Conserved Chromatin Signature in Intron 3

Barthel, Robert; Goldfeld, Anne E.

doi:10.4049/jimmunol.171.7.3612

Cited by 27 publications

(41 citation statements)

References 28 publications

(33 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…First, our targeting design may have removed a regulatory element controlling transcription of the LT genes. Indeed, transcriptional enhancers have been identified in the third intron of the TNF gene [41][42][43] and in its downstream region [44], although there is no evidence that these enhancers may affect LT gene expression; importantly, we did not observe any gross LT deregulation on lymphocytes from TNF D/D mice. Alternatively, an actively transcribed neo cassette, which is retained in the TNF/LT locus in all reported conventional TNF-KO mice, may cause compensatory up-regulation of the neighboring LT genes, resulting in elevated signaling either by LTa 3 via TNFR1 or by LTb 2 LTa 1 via LTbR.…”

Section: Discussionmentioning

confidence: 45%

Novel tumor necrosis factor‐knockout mice that lack Peyer's patches

et al. 2005

View full text Add to dashboard Cite

We generated a novel tumor necrosis factor (TNF) null mutation using Cre-loxP technology. Mice homozygous for this mutation differ from their "conventional" counterparts; in particular, they completely lack Peyer's patches (PP) but retain all lymph nodes. Our analysis of these novel TNF-knockout mice supports the previously disputed notion of the involvement of TNF-TNFR1 signaling in PP organogenesis. Availability of TNF-knockout strains both with and without PP enables more definitive studies concerning the roles of TNF and PP in various immune functions and disease conditions. Here, we report that systemic ablation of TNF, but not the presence of PP per se, is critical for protection against intestinal Listeria infection in mice.

show abstract

Section: Discussionmentioning

confidence: 45%

Novel tumor necrosis factor‐knockout mice that lack Peyer's patches

et al. 2005

View full text Add to dashboard Cite

show abstract

“…A precedent for inducer and cell-type-specific regulation and recruitment of distinct activator complexes has been described for the TNF gene (26,34), for which a DNase I HSS has been detected in T cells but not in monocytic cell lines (35). Differential DNase I patterns were also shown for the IL-4 locus in mast cells vs T cells (36).…”

Section: Discussionmentioning

confidence: 92%

Identification of a Macrophage-Specific Chromatin Signature in the IL-10 Locus

Saraiva¹,

Christensen²,

Tsytsykova

et al. 2005

The Journal of Immunology

Self Cite

106

View full text Add to dashboard Cite

The molecular mechanisms that regulate expression of the immunosuppressive cytokine IL-10 remain poorly understood. In this study, by measuring sensitivity to DNase I digestion, we show that production of IL-10 by primary mouse bone marrow-derived macrophages stimulated through pattern recognition receptors was associated with chromatin remodeling of the IL-10 locus. We also demonstrate that the IL-10 locus is remodeled in primary Th2 cells and IL-10-producing regulatory T cells that have been differentiated in vitro. Strikingly, a novel DNase I-hypersensitive site (HSS-4.5) was identified in stimulated macrophages, but not in T cells. We show that hyperacetylated histones were recruited to this site in stimulated macrophages. Furthermore, HSS-4.5 is highly conserved and contains a putative NF-κB binding site. In support of a function for this site, NF-κB p65/RelA was recruited to HSS-4.5 in vivo and its activation was required for optimal IL-10 gene expression in LPS-stimulated macrophages.

show abstract

“…A growing body of evidence demonstrates that chromatin modification is another important mechanism that regulates cytokine expression (Barth and Imhof 2010;Bartova et al 2008;Kouzarides 2007;Strahl and Allis 2000). Many immune related genes such as MCP-1, TNF-α, IL-12, and IL-4 are regulated by epigenetic changes characterized by histone metylation and acetylation (Weinmann et al 1999;Fields et al 2002;Barthel and Goldfeld 2003;Boekhoudt et al 2003;Goriely et al 2003;Wen et al 2008). Furthermore, TLRinduced chromatin modification of H3K4me3 and histone acetylation are shown to control the inflammation by silencing the pro-inflammatory mediators (Foster et al 2007).…”

Section: Discussionmentioning

confidence: 99%

Impaired secretion of interferons by dendritic cells from aged subjects to influenza

Prakash

Agrawal

Cao

et al. 2012

AGE

View full text Add to dashboard Cite

Increased susceptibility to respiratory infections such as influenza is the hallmark of advancing age. The mechanisms underlying the impaired immune response to influenza are not well understood. In the present study, we have investigated the effect of advancing age on dendritic cell (DC) function because they are critical in generating robust antiviral responses. Our results indicate that monocyte derived DCs from the aged are impaired in their capacity to secrete interferon (IFN)-I in response to influenza virus. Additionally, we observed a severe reduction in the production of IFN-III, which plays an important role in defense against viral infections at respiratory mucosal surfaces. This reduction in IFN-I and IFN-III were a result of age-associated modifications in the chromatin structure. Investigations using chromatin immunoprecipitation with H3K4me3 and H3K9me3 antibodies revealed that there is increased association of IFN-I and IFN-III promoters with the repressor histone, H3K9me3 in non-stimulated aged DCs compared to young DCs. This was accompanied by decreased association of these promoters with activator histone, H3K4me3 in aged DCs after activation with influenza. In contrast to interferons, the association of TNF-alpha promoter with both these histones was comparable between aged and young subjects. Investigations at 48 h suggested that these changes are not stable and change with time. In summary, our study demonstrates that myeloid DCs from aged subjects are impaired in their capacity to produce IFNs in response to influenza virus and that age-associated altered histone expression patterns are responsible for the decrease in IFN production.

show abstract

T Cell-Specific Expression of the Human TNF-α Gene Involves a Functional and Highly Conserved Chromatin Signature in Intron 3

Cited by 27 publications

References 28 publications

Novel tumor necrosis factor‐knockout mice that lack Peyer's patches

Novel tumor necrosis factor‐knockout mice that lack Peyer's patches

Identification of a Macrophage-Specific Chromatin Signature in the IL-10 Locus

Impaired secretion of interferons by dendritic cells from aged subjects to influenza

Contact Info

Product

Resources

About