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101.
Many organisms are capable of developing distinct phenotypes from the same genotype. This developmental plasticity is particularly prevalent in insects, which can produce alternate adaptive forms in response to distinct environmental cues. The ability to develop divergent phenotypes from the same genotype often relies on epigenetic information, which affects gene function and is transmitted through cell divisions. One of the most important epigenetic marks, DNA methylation, has been lost in several insect lineages, yet its taxonomic distribution and functional conservation remain uninvestigated in many taxa. In the present study, we demonstrate that the signature of high levels of DNA methylation exists in the expressed genes of two termites, Reticulitermes flavipes and Coptotermes formosanus. Further, we show that DNA methylation is preferentially targeted to genes with ubiquitous expression among morphs. Functional associations of DNA methylation are also similar to those observed in other invertebrate taxa with functional DNA methylation systems. Finally, we demonstrate an association between DNA methylation and the long‐term evolutionary conservation of genes. Overall, our findings strongly suggest DNA methylation is present at particularly high levels in termites and may play similar roles to those found in other insects. 相似文献
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Epigenome‐wide DNA methylation changes with development of arsenic‐induced skin lesions in Bangladesh: A case–control follow‐up study 下载免费PDF全文
Wei Jie Seow Molly L. Kile Andrea A. Baccarelli Wen‐Chi Pan Hyang‐Min Byun Golam Mostofa Quazi Quamruzzaman Mahmuder Rahman Xihong Lin David C. Christiani 《Environmental and molecular mutagenesis》2014,55(6):449-456
Studies have found an association between aberrant DNA methylation and arsenic‐induced skin lesions. However, little is known about DNA methylation changes over time in people who develop arsenic‐induced skin lesions. We sought to investigate epigenome‐wide changes of DNA methylation in people who developed arsenic‐induced skin lesions in a 10‐year period. In 2009–2011, we conducted a follow‐up study of 900 skin lesion cases and 900 controls and identified 10 people who developed skin lesions since a baseline survey in 2001–2003. The 10 cases (“New Cases”) were matched with 10 controls who did not have skin lesions at baseline or follow‐up (“Persistent Controls”). Drinking water and blood samples were collected, and skin lesion was diagnosed by the same physician at both time points. We measured DNA methylation in blood using Infinium HumanMethylation450K BeadChip, followed by quantitative validation using pyrosequencing. Two‐sample t‐tests were used to compare changes in percent methylation between New Cases and Persistent Controls. Six CpG (cytosine‐phosphate‐guanine) sites with greatest changes of DNA methylation over time among New Cases were further validated with a correlation of 93% using pyrosequencing. One of the validated CpG site (cg03333116; change of %methylation was 13.2 in New Cases versus ?0.09 in Persistent Controls; P < 0.001) belonged to the RHBDF1 gene, which was previously reported to be hypermethylated in arsenic‐exposed cases. We examined DNA methylation changes with the development of arsenic‐induced skin lesions over time but nothing was statistically significant given the small sample size of this exploratory study and the high dimensionality of data. Environ. Mol. Mutagen. 55:449–456, 2014. © 2014 Wiley Periodicals, Inc. 相似文献
104.
树突状细胞(DCs)是体内功能最强的专职抗原提呈细胞,具有摄取、加工、处理和呈递抗原以及激活初始T淋巴细胞的功能。近年来研究发现,DNA甲基化、组蛋白修饰、染色质重塑、基因组印记以及非编码RNA等表观遗传学修饰能调控相关基因的表达,同时树突状细胞的分化发育及功能也受到表观遗传学调控。研究从DNA甲基化修饰、组蛋白修饰和非编码RNA,了解近年来很有必要树突状细胞的分化发育及功能的表观遗传学调控机制很有意义。 相似文献
105.
High pesticide exposure events and DNA methylation among pesticide applicators in the agricultural health study 下载免费PDF全文
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Csepregi A Röcken C Hoffmann J Gu P Saliger S Müller O Schneider-Stock R Kutzner N Roessner A Malfertheiner P Ebert MP 《Journal of cancer research and clinical oncology》2008,134(5):579-589
Purpose We investigated the impact of promoter methylation on APC protein expression in patients with hepatocellular carcinoma (HCC).
Materials and methods 50 patients [HCC (n=19), liver metastasis (n=19), cholangiocellular cancer (n=7), and benign liver tumors (n=5)] were studied
for methylation using Methylight analysis. APC mutation was investigated by protein truncation test and direct sequencing
of genomic DNA. The protein expression was evaluated by immunohistochemistry and Western blot analysis.
Results The APC promoter was hypermethylated in 81.8% of non-cancerous liver tissue samples. All HCC samples and ten patients with
liver metastasis (52.6%) exhibited APC promoter methylation. The degree of methylation was significantly higher in samples
from HCC compared to the non-cancerous liver tissue samples (63.1% vs. 24.98%; p=0.001). The level of APC protein expression
was significantly reduced in HCC samples compared to that of the corresponding non-tumor liver tissue (p<0.05).
Conclusions Promoter methylation of the APC gene seems to be of significance in hepatocarcinogenesis and results in reduced protein expression
in HCC. Interestingly, APC promoter methylation is also present in the vast majority of non-cancerous liver tissue whose (patho)physiological
function remains unresolved. 相似文献
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Renáta Váraljai Abul B.M.M.K. Islam Michael L. Beshiri Jalees Rehman Nuria Lopez-Bigas Elizaveta V. Benevolenskaya 《Genes & development》2015,29(17):1817-1834
The retinoblastoma tumor suppressor protein pRb restricts cell growth through inhibition of cell cycle progression. Increasing evidence suggests that pRb also promotes differentiation, but the mechanisms are poorly understood, and the key question remains as to how differentiation in tumor cells can be enhanced in order to diminish their aggressive potential. Previously, we identified the histone demethylase KDM5A (lysine [K]-specific demethylase 5A), which demethylates histone H3 on Lys4 (H3K4), as a pRB-interacting protein counteracting pRB''s role in promoting differentiation. Here we show that loss of Kdm5a restores differentiation through increasing mitochondrial respiration. This metabolic effect is both necessary and sufficient to induce the expression of a network of cell type-specific signaling and structural genes. Importantly, the regulatory functions of pRB in the cell cycle and differentiation are distinct because although restoring differentiation requires intact mitochondrial function, it does not necessitate cell cycle exit. Cells lacking Rb1 exhibit defective mitochondria and decreased oxygen consumption. Kdm5a is a direct repressor of metabolic regulatory genes, thus explaining the compensatory role of Kdm5a deletion in restoring mitochondrial function and differentiation. Significantly, activation of mitochondrial function by the mitochondrial biogenesis regulator Pgc-1α (peroxisome proliferator-activated receptor γ-coactivator 1α; also called PPARGC1A) a coactivator of the Kdm5a target genes, is sufficient to override the differentiation block. Overexpression of Pgc-1α, like KDM5A deletion, inhibits cell growth in RB-negative human cancer cell lines. The rescue of differentiation by loss of KDM5A or by activation of mitochondrial biogenesis reveals the switch to oxidative phosphorylation as an essential step in restoring differentiation and a less aggressive cancer phenotype. 相似文献