Global Histone H3K27 Methylation Levels are Different in Localized and Metastatic Prostate Cancer

Ellinger, Jörg; Kahl, Philip; Gathen, Johannes von der; Heukamp, Lukas C.; Gütgemann, Ines; Walter, Bernhard; Hofstädter, Ferdinand; Bastian, Patrick J.; Ruecker, Alexander von; Müller, Stefan; Rogenhofer, Sebastian

doi:10.3109/07357907.2011.636117

Cited by 50 publications

(38 citation statements)

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“…Dysregulation of H3K27me3 has also been implicated in the genesis and progression of cancer (Chi et al 2010; Ellinger et al 2012). These results indicate that H3K27me3 plays a role in the creation and maintenance of cell type-specific programs of transcriptional control for a wide variety of species and cell fates.…”

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confidence: 51%

Evolution of H3K27me3-marked chromatin is linked to gene expression evolution and to patterns of gene duplication and diversification

Arthur

Slattery

et al. 2014

Genome Res.

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Histone modifications are critical for the regulation of gene expression, cell type specification, and differentiation. However, evolutionary patterns of key modifications that regulate gene expression in differentiating organisms have not been examined. Here we mapped the genomic locations of the repressive mark histone 3 lysine 27 trimethylation (H3K27me3) in four species of Drosophila, and compared these patterns to those in C. elegans. We found that patterns of H3K27me3 are highly conserved across species, but conservation is substantially weaker among duplicated genes. We further discovered that retropositions are associated with greater evolutionary changes in H3K27me3 and gene expression than tandem duplications, indicating that local chromatin constraints influence duplicated gene evolution. These changes are also associated with concomitant evolution of gene expression. Our findings reveal the strong conservation of genomic architecture governed by an epigenetic mark across distantly related species and the importance of gene duplication in generating novel H3K27me3 profiles.[Supplemental material is available for this article.]While transcriptional regulation has long been recognized as a significant target of evolutionary change (King and Wilson 1975), the specific mechanisms behind regulatory divergence have been difficult to dissect (Carroll 2008). In most cases, research has focused on recognizable cis-elements where transcription factors bind in a sequence-specific manner (Borneman et al. 2007;Bradley et al. 2010;Dowell 2010;Ni et al. 2012). Changes to either a transcription factor's DNA-binding properties or transcription factor binding sites (TFBS) enable the evolution of differential regulation, and numerous examples of this phenomenon have been observed (Ludwig et al. 2005;Shultzaberger et al. 2012).Whereas changes in cis-regulatory elements have been implicated in phenotypic and specifically morphological changes (Carroll 2008;Stern and Orgogozo 2008), other components of transcriptional regulation such as the chromatin environment have been scarcely explored (Lenhard et al. 2012). Histone modifications, which are chemical alterations of the histone spools upon which DNA is threaded, constitute one of the best-described elements of chromatin state (Zhou et al. 2011). These modifications can act directly or indirectly (through recruited enzymes) to alter DNA accessibility, thereby controlling other DNA-protein interactions (Campos and Reinberg 2009). Unlike TFBSs, however, histone modifications are not necessarily easily localizable to particular sequence elements, making their evolution difficult to study (Delest et al. 2012).Histone 3 lysine 27 trimethylation (H3K27me3) is one of the best-known histone modifications, in terms of both its biogenesis and effects. H3K27me3 is associated with complex cis-regulatory elements called Polycomb Response Elements (PREs) (Delest et al. 2012). Unlike TFBSs, PREs are compound regulatory elements composed of multiple, sometimes partially redundant, sequen...

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confidence: 51%

Evolution of H3K27me3-marked chromatin is linked to gene expression evolution and to patterns of gene duplication and diversification

Arthur

Slattery

et al. 2014

Genome Res.

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“…At least 5 high-power fields and more than 2,000 cells were calculated in each case with a light microscope (Zeiss 2021-85; Carl Zeiss Inc.) at x400 magnification. Immunostaining results were evaluated by using a semi-quantitative scoring system according to the method described in the study by Ellinger et al (15). That is, the number of positive cancerous cells was estimated as follows (0, no positive cells; 1, 0> and ≤25% positive cells; 2, >25 and ≤50% positive cells; 3, >50 and ≤75% positive cells; and 4, >75 and ≤100% positive cells).…”

Section: Methodsmentioning

confidence: 99%

High expression of trimethylated histone H3 at lysine 27 predicts better prognosis in non-small cell lung cancer

Chen

Song

Matsumoto

et al. 2013

International Journal of Oncology

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Abstract. Epigenetic parameters such as DNA methylation and histone modifications play pivotal roles in carcinogenesis. Global histone modification patterns have been implicated as possible predictors of cancer recurrence and prognoses in a great variety of tumor entities. Our study was designed to evaluate the association among trimethylated histone H3 at lysine 27 (H3K27me3), clinicopathological variables and outcome in early-stage non-small cell lung cancer (NSCLC). The expression of H3K27me3 and its methyl transferase, enhancer of zeste homolog 2 (EZH2) together with proliferating cell nuclear antigen (PCNA) were evaluated by immunohistochemistry in normal lung tissue (n=5) and resected NSCLC patients (n=42). In addition, the specificity of antibody for H3K27me3 was tested by western blot analysis. The optimal cut-off point of H3K27me3 expression for prognosis was determined by the X-tile program. The prognostic significance was determined by means of KaplanMeier survival estimates and log-rank tests. As a result, enhanced trimethylation of H3K27me3 was correlated with longer overall survival (OS) and better prognosis (P<0.05). Moreover, both univariate and multivariate analyses indicated that H3K27me3 level was a significant and independent predictor of better survival (hazard ratio, 0.187; 95% confidence interval, 0.066-0.531, P= 0.002). Furthermore, H3K27me3 expression was positively correlated with DNA methylation level at CCGG sites while reversely related to EZH2 expression (P<0.05). In conclusion, H3K27me3 level defines unrecognized subgroups of NSCLC patients with distinct epigenetic phenotype and clinical outcome, and can probably be used as a novel predictor for better prognosis in NSCLC patients.

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“…Immunohistochemical analysis of H3K9 [11] and H3K27 [12] methylation had been described before, and the experimental protocol was adopted for this study. In brief, paraffin sections (5 µm) were cut from the tissue microarray block, deparaffinized using xylene and rehydrated with graded ethanol.…”

Section: Methodsmentioning

confidence: 99%

“…These histone modifications allowed differentiation of normal and malignant tissue in various urological malignancies (e.g. H3K9 and H3K27 methylation: penile carcinoma [10]; prostate cancer [11,12,13]; renal cell carcinoma [14,15,16]), and prognostic relevance was also reported for specific modifications of H3K9 and H3K27 in renal cell carcinoma (H3K9me1 [14] and H3K27me score [15]), prostate cancer [6,17] and many other non-urological tumor entities (e.g. non-small cell lung cancer and gastric cancer, H3K9me3 [18,19]; colorectal cancer, H3K27me2 [20]; breast cancer, H3K27me3 [21]).…”

Section: Introductionmentioning

confidence: 99%

Alterations of Global Histone H3K9 and H3K27 Methylation Levels in Bladder Cancer

et al. 2014

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Background: Epigenetic alterations, including histone modifications, play an important role during carcinogenesis. This study was designed to systematically investigate histone H3K9 and H3K27 methylation levels in bladder cancer (BCa) tissue. Methods: A tissue microarray with urothelial BCa (150 non-muscle-invasive BCa, NMIBC; 121 muscle-invasive BCa, MIBC; 31 metastatic BCa, MET) and normal urothelium (29, CTRL) specimen was used to determine the global levels of H3K9 and H3K27 mono-, di- and tri-methylation. Results: Global levels of H3K9 and H3K27 methylation were significantly higher in CTRL than in BCa, and levels in NMIBC were higher compared to MIBC. Histone methylation levels of MET resembled MIBC. We observed furthermore a correlation of histone methylation levels with pT stage (H3K9me1, H3K9me2, H3K9me3, H3K27me1, H3K27me3) and grade (H3K9me2, H3K9me3, H3K27me1) in NMIBC. H3K9me1, H3K9me3, H3K27me1 and H3K27me3 levels were also correlated with pT stage in MIBC. Histone modifications were not associated with recurrence-free or cancer-specific survival. Conclusions: Global histone H3K9 and H3K27 methylation levels are altered in BCa.

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Global Histone H3K27 Methylation Levels are Different in Localized and Metastatic Prostate Cancer

Cited by 50 publications

References 25 publications

Evolution of H3K27me3-marked chromatin is linked to gene expression evolution and to patterns of gene duplication and diversification

Evolution of H3K27me3-marked chromatin is linked to gene expression evolution and to patterns of gene duplication and diversification

High expression of trimethylated histone H3 at lysine 27 predicts better prognosis in non-small cell lung cancer

Alterations of Global Histone H3K9 and H3K27 Methylation Levels in Bladder Cancer

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