Immunohistochemical Analysis of Histone H3 Modifications in Germ Cells during Mouse Spermatogenesis

Song, Ning; Liu, Jie; An, Shucai; Nishino, Tomoya; Hishikawa, Yoshitaka; Koji, Takehiko

doi:10.1267/ahc.11027

Cited by 132 publications

(108 citation statements)

References 33 publications

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“…Immunohistochemistry was performed with the indirect enzyme-labeled antibody method, as described previously (31)(32)(33). Antibodies used in IHC are listed in Table II.…”

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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“…Immunohistochemistry was performed with the indirect enzyme-labeled antibody method, as described previously (31)(32)(33). Antibodies used in IHC are listed in Table II.…”

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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“…In addition, during spermatogenesis, the chromatin structure in the cells and the expression pattern of ncRNA are dramatically remodeled (Ro et al 2007, Song et al 2011, Shirakata et al 2014. The extensive time from prospermatogonia to final mature sperm cell (decades in humans) represents a risk for DNA methylation changes to accumulate.…”

Section: R44 L R H Illum Et Almentioning

confidence: 99%

DNA methylation in epigenetic inheritance of metabolic diseases through the male germ line

Illum

Bak

Lund

et al. 2018

Journal of Molecular Endocrinology

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The global rise in metabolic diseases can be attributed to a complex interplay between biology, behavior and environmental factors. This article reviews the current literature concerning DNA methylation-based epigenetic inheritance (intergenerational and transgenerational) of metabolic diseases through the male germ line. Included are a presentation of the basic principles for DNA methylation in developmental programming, and a description of windows of susceptibility for the inheritance of environmentally induced aberrations in DNA methylation and their associated metabolic disease phenotypes. To this end, escapees, genomic regions with the intrinsic potential to transmit acquired paternal epigenetic information across generations by escaping the extensive programmed DNA demethylation that occurs during gametogenesis and in the zygote, are described. The ongoing descriptive and functional examinations of DNA methylation in the relevant biological samples, in conjugation with analyses of noncoding RNA and histone modifications, hold promise for improved delineation of the effect size and mechanistic background for epigenetic inheritance of metabolic diseases.

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“…Loose protein structure stimulates DNA strand breaks caused by topoisomerase enzyme, and facilitates separation of histones, and their replacement by transition proteins (TPs). [43,44] Hyperacetylation triggers chain of events with resultant replacement of histones by protamines. [45] Transition proteins 1, and 2 demonstrate moderately basic non-histone proteins.…”

Section: Modification Of Chromatin During Spermatogenesismentioning

confidence: 99%

The role of epigenetics in spermatogenesis

Güneş

Kulac

2014

Turkish Journal of Urology

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Male germ cells have a unique morphology and function to facilitate fertilization. Sperm deoxyribonucleic acid (DNA) is highly condensed to protect the paternal genome during transfer from male to oocyte. Sperm cells undergo extensive epigenetic modifications during differentiation to become a mature spermatozoon. Epigenetic modifications, including DNA methylation, histone modifications, and chromatin remodeling are substantial regulators of spermatogenesis. DNA hypermethylation is associated with gene silencing. Meanwhile, hypomethylation is associated with gene expression. In sperm cells, promoters of developmental genes are highly hypomethylated. Proper DNA methylation is essential for embryo development. Histone modifications are chemical modifications that change the DNA-binding capacity of histones and the accessibility of regulatory factors to the DNA, thereby altering gene expression. Phosphorylation, methylation, acetylation, and ubiquitination are primary modifications of lysine and serine residues on histone tails. In addition to somatic histones, testis-specific histone variants are expressed, including histone H2B in mature sperm. The replacement of histones with protamines is a crucial step in spermatogenesis. Histone hyperacetylation induces a loose chromatin structure and facilitates topoisomerase-induced DNA strand breaks. As a result, histones are replaced with transition proteins. Next, the transition proteins are replaced with protamines that induce compaction of sperm DNA. This review provides an overview of epigenetic changes during spermatogenesis.

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Immunohistochemical Analysis of Histone H3 Modifications in Germ Cells during Mouse Spermatogenesis

Cited by 132 publications

References 33 publications

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

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

DNA methylation in epigenetic inheritance of metabolic diseases through the male germ line

The role of epigenetics in spermatogenesis

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