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Differential patterns of histone acetylation in inflammatory bowel diseases.

Tsaprouni LG, Ito K, Powell JJ, Adcock IM, Punchard N - J Inflamm (Lond) (2011)

Bottom Line: Post-translational modifications of histones, particularly acetylation, are associated with the regulation of inflammatory gene expression.Acetylation of histone H4 was significantly elevated in the inflamed mucosa in the trinitrobenzene sulfonic acid model of colitis particularly on lysine residues (K) 8 and 12 in contrast to non-inflamed tissue.These results demonstrate that histone acetylation is associated with inflammation and may provide a novel therapeutic target for mucosal inflammation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Airways Disease Section, National Heart & Lung Institute, Imperial College London, Dovehouse Street, London, SW3 6LY, UK. ian.adcock@imperial.ac.uk.

ABSTRACT
Post-translational modifications of histones, particularly acetylation, are associated with the regulation of inflammatory gene expression. We used two animal models of inflammation of the bowel and biopsy samples from patients with Crohn's disease (CD) to study the expression of acetylated histones (H) 3 and 4 in inflamed mucosa. Acetylation of histone H4 was significantly elevated in the inflamed mucosa in the trinitrobenzene sulfonic acid model of colitis particularly on lysine residues (K) 8 and 12 in contrast to non-inflamed tissue. In addition, acetylated H4 was localised to inflamed tissue and to Peyer's patches (PP) in dextran sulfate sodium (DSS)-treated rat models. Within the PP, H3 acetylation was detected in the mantle zone whereas H4 acetylation was seen in both the periphery and the germinal centre. Finally, acetylation of H4 was significantly upregulated in inflamed biopsies and PP from patients with CD. Enhanced acetylation of H4K5 and K16 was seen in the PP. These results demonstrate that histone acetylation is associated with inflammation and may provide a novel therapeutic target for mucosal inflammation.

No MeSH data available.


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Acetylation on histone 4 (H4) and H4 lysine residues in Crohn's disease. Columns represent the mean ± SEM of three independent experiments. Four biopsies were pooled to obtain sufficient protein for one experiment (50 μg of protein) (*p < 0.05 vs control). Pan acetylation on H4 in Crohn's disease (A). Acetylation on histone 4 (H4) specific lysine residues 5 (K5) (B), K8 (C), K12 (D), and 16 (E), in non-inflamed, inflamed tissue and Peyer's patches of Crohn's disease patients. Results were obtained by Western blotting. Columns represent the mean ± SEM of three independent experiments. (*p < 0.05 vs control, #p < 0.005 vs non-inflamed CD). Representative images of the bands obtained are illustrated.
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Figure 5: Acetylation on histone 4 (H4) and H4 lysine residues in Crohn's disease. Columns represent the mean ± SEM of three independent experiments. Four biopsies were pooled to obtain sufficient protein for one experiment (50 μg of protein) (*p < 0.05 vs control). Pan acetylation on H4 in Crohn's disease (A). Acetylation on histone 4 (H4) specific lysine residues 5 (K5) (B), K8 (C), K12 (D), and 16 (E), in non-inflamed, inflamed tissue and Peyer's patches of Crohn's disease patients. Results were obtained by Western blotting. Columns represent the mean ± SEM of three independent experiments. (*p < 0.05 vs control, #p < 0.005 vs non-inflamed CD). Representative images of the bands obtained are illustrated.

Mentions: Acetylation on H4 was slightly induced in the non-inflamed ileum of Crohn's disease patients. In contrast, H4 acetylation was significantly elevated in the inflamed regions (472 ± 88 vs 100 ± 34% control, p < 0.05) (Figure 5A). Peyer's patches from Crohn's disease patients also showed a significant increase in pan H4 acetylation (382 ± 29%) compared to the control non-inflamed tissue (100 ± 34%, p < 0.05) (Figure 5A). Levels of acetylated K5 were not significantly upregulated compared to control (Figure 5). More specifically, K8 acetylation was significantly induced compared to control samples in the inflamed regions (527 ± 44% vs 100 ± 25% control tissue, p < 0.05) and the non-inflamed CD samples (527 ± 44% vs 195 ± 42% non-inflamed CD, p < 0.05). In Peyer's patches from CD patients, K8 was significantly upregulated compared to control (488 ± 52% vs 100 ± 25% control tissue, p < 0.05) (Figure 5).


Differential patterns of histone acetylation in inflammatory bowel diseases.

Tsaprouni LG, Ito K, Powell JJ, Adcock IM, Punchard N - J Inflamm (Lond) (2011)

Acetylation on histone 4 (H4) and H4 lysine residues in Crohn's disease. Columns represent the mean ± SEM of three independent experiments. Four biopsies were pooled to obtain sufficient protein for one experiment (50 μg of protein) (*p < 0.05 vs control). Pan acetylation on H4 in Crohn's disease (A). Acetylation on histone 4 (H4) specific lysine residues 5 (K5) (B), K8 (C), K12 (D), and 16 (E), in non-inflamed, inflamed tissue and Peyer's patches of Crohn's disease patients. Results were obtained by Western blotting. Columns represent the mean ± SEM of three independent experiments. (*p < 0.05 vs control, #p < 0.005 vs non-inflamed CD). Representative images of the bands obtained are illustrated.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3040698&req=5

Figure 5: Acetylation on histone 4 (H4) and H4 lysine residues in Crohn's disease. Columns represent the mean ± SEM of three independent experiments. Four biopsies were pooled to obtain sufficient protein for one experiment (50 μg of protein) (*p < 0.05 vs control). Pan acetylation on H4 in Crohn's disease (A). Acetylation on histone 4 (H4) specific lysine residues 5 (K5) (B), K8 (C), K12 (D), and 16 (E), in non-inflamed, inflamed tissue and Peyer's patches of Crohn's disease patients. Results were obtained by Western blotting. Columns represent the mean ± SEM of three independent experiments. (*p < 0.05 vs control, #p < 0.005 vs non-inflamed CD). Representative images of the bands obtained are illustrated.
Mentions: Acetylation on H4 was slightly induced in the non-inflamed ileum of Crohn's disease patients. In contrast, H4 acetylation was significantly elevated in the inflamed regions (472 ± 88 vs 100 ± 34% control, p < 0.05) (Figure 5A). Peyer's patches from Crohn's disease patients also showed a significant increase in pan H4 acetylation (382 ± 29%) compared to the control non-inflamed tissue (100 ± 34%, p < 0.05) (Figure 5A). Levels of acetylated K5 were not significantly upregulated compared to control (Figure 5). More specifically, K8 acetylation was significantly induced compared to control samples in the inflamed regions (527 ± 44% vs 100 ± 25% control tissue, p < 0.05) and the non-inflamed CD samples (527 ± 44% vs 195 ± 42% non-inflamed CD, p < 0.05). In Peyer's patches from CD patients, K8 was significantly upregulated compared to control (488 ± 52% vs 100 ± 25% control tissue, p < 0.05) (Figure 5).

Bottom Line: Post-translational modifications of histones, particularly acetylation, are associated with the regulation of inflammatory gene expression.Acetylation of histone H4 was significantly elevated in the inflamed mucosa in the trinitrobenzene sulfonic acid model of colitis particularly on lysine residues (K) 8 and 12 in contrast to non-inflamed tissue.These results demonstrate that histone acetylation is associated with inflammation and may provide a novel therapeutic target for mucosal inflammation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Airways Disease Section, National Heart & Lung Institute, Imperial College London, Dovehouse Street, London, SW3 6LY, UK. ian.adcock@imperial.ac.uk.

ABSTRACT
Post-translational modifications of histones, particularly acetylation, are associated with the regulation of inflammatory gene expression. We used two animal models of inflammation of the bowel and biopsy samples from patients with Crohn's disease (CD) to study the expression of acetylated histones (H) 3 and 4 in inflamed mucosa. Acetylation of histone H4 was significantly elevated in the inflamed mucosa in the trinitrobenzene sulfonic acid model of colitis particularly on lysine residues (K) 8 and 12 in contrast to non-inflamed tissue. In addition, acetylated H4 was localised to inflamed tissue and to Peyer's patches (PP) in dextran sulfate sodium (DSS)-treated rat models. Within the PP, H3 acetylation was detected in the mantle zone whereas H4 acetylation was seen in both the periphery and the germinal centre. Finally, acetylation of H4 was significantly upregulated in inflamed biopsies and PP from patients with CD. Enhanced acetylation of H4K5 and K16 was seen in the PP. These results demonstrate that histone acetylation is associated with inflammation and may provide a novel therapeutic target for mucosal inflammation.

No MeSH data available.


Related in: MedlinePlus