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#33278554   2020/12/03 To Up

Identification of DNA (de)methylation-related genes and their transcriptional response to environmental challenges in an invasive model ascidian.

Marine invasive species are constantly challenged by acute or recurring environmental stresses during their range expansions. DNA methylation-mediated stress memory has been proposed to effectively affect species' response and enhance their overall performance in recurring environmental challenges. In order to further test this proposal in marine invasive species, we identified genes in the DNA methylation and demethylation processes in the highly invasive model species, Ciona robusta, and subsequently investigated the expression patterns of these genes under recurring salinity stresses. After a genome-wide comprehensive survey, we found a total of six genes, including two genes of DNA methyltransferase 3a (DNMT3a1 and DNMT3a2), and one gene of DNA methyltransferase 1 (DNMT1), methyl-CpG-binding domain protein 2 (MBD2), methyl-CpG-binding domain protein 4 (MBD4) and ten-eleven-translocation protein 1 (TET1). Phylogenetic reconstruction and domain arrangement analyses showed that the deduced proteins of the identified genes were evolutionarily conserved and functionally similar with their orthologs. All genes were constitutively expressed in all four tested tissues. Interestingly, we found time-dependent and stress-specific gene expression patterns under high and low salinity stresses. Under the recurring high salinity stresses, DNMT3a1 and TET1 conformed to the definition of memory genes, while under the recurring low salinity stresses, two DNMT3a paralogues were identified as the memory genes. Altogether, our results clearly showed that the transcriptional patterns of (de)methylation-related genes were significantly influenced by environmental stresses, and the transcriptional memory of some (de)methylation-related genes should play crucial roles in DNA methylation-mediated stress memory during the process of biological invasions.
Ruiying Fu, Xuena Huang, Aibin Zhan

2190 related Products with: Identification of DNA (de)methylation-related genes and their transcriptional response to environmental challenges in an invasive model ascidian.

100 2 Pieces/Box 100 UG1 mg2 Pieces/Box100 μg2 Pieces/Box

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#32850324   2020/07/30 To Up

Methylation-Induced Silencing of ALDH2 Facilitates Lung Adenocarcinoma Bone Metastasis by Activating the MAPK Pathway.

Bone metastasis (BM) dramatically reduces the quality of life and life expectancy in lung adenocarcinoma (LUAD) patients. There is an urgent need to identify potential biomarkers for application in the treatment of this deadly disease. We compared patient BM, LUAD, and para-LUAD tissues using proteomic analysis and identified aldehyde dehydrogenase 2 (ALDH2), which can detoxify acetaldehyde to acetic acid, as one of the key regulators in lung tumor metastasis. Both the mRNA and protein levels of ALDH2 were significantly lower in tumor tissues than in normal tissues and were lowest in BM tissues with increased migratory capacity. Also, ALDH2 was upregulated following treatment with 5-azacitidine, a DNA methyltransferase inhibitor, in H1299, H460, and HCC827 cells. Further, we identified a potential methylated CpG island 3, with the longest methylated CpG island area in ALDH2, and performed bisulfite genomic sequencing of these sites. An average of 78.18% of the sites may be methylated in CpG island 3. Knockdown of DNA (cytosine-5)-methyltransferase 3A (DNMT3A) and methylated CpG binding protein 4 (MBD4) upregulated ALDH2 expression. ALDH2 functions as a mitogen-activated protein kinase (MAPK) upstream to inhibit cell proliferation and migration, promote cell apoptosis, and alter the epithelial-mesenchymal transition (EMT) by elevating E-cadherin and attenuating vimentin. Cell proliferation and migration were inhibited after the addition of the JNK inhibitor SP600125. In the multivariate analysis, M stage ( = 0.003), ALDH2 ( = 0.008), and phospho-c-Jun N-terminal kinase (p-JNK) ( = 0.027) expression were independent prognostic factors for overall survival in patients with BM. experiments also showed that ALDH2 expression could suppress tumor formation. In summary, we found that ALDH2 expression is a prognostic factor for BM in LUAD and that DNMT3A and MBD4 repression of ALDH2 via a MAPK-dependent pathway alters the EMT process, indicating that these proteins could act as potential biomarkers or therapeutic targets for LUAD metastasis.
Mengdi Yang, AiTing Wang, Changcan Li, Jing Sun, Gang Yi, Hao Cheng, Xueni Liu, Zhiyu Wang, Yiyi Zhou, Guangyu Yao, Shuai Wang, Rui Liang, Bin Li, Dan Li, Hui Zhao

1161 related Products with: Methylation-Induced Silencing of ALDH2 Facilitates Lung Adenocarcinoma Bone Metastasis by Activating the MAPK Pathway.

50 ul2 Pieces/Box100 ul

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#32748830   2020/08/02 To Up

An EPR Study on the Interaction between the Cu(I) Metal Binding Domains of ATP7B and the Atox1 Metallochaperone.

Copper's essentiality and toxicity mean it requires a sophisticated regulation system for its acquisition, cellular distribution and excretion, which until now has remained elusive. Herein, we applied continuous wave (CW) and pulsed electron paramagnetic resonance (EPR) spectroscopy in solution to resolve the copper trafficking mechanism in humans, by considering the route travelled by Cu(I) from the metallochaperone Atox1 to the metal binding domains of ATP7B. Our study revealed that Cu(I) is most likely mediated by the binding of the Atox1 monomer to metal binding domain 1 (MBD1) and MBD4 of ATP7B in the final part of its extraction pathway, while the other MBDs mediate this interaction and participate in copper transfer between the various MBDs to the ATP7B membrane domain. This research also proposes that MBD1-3 and MBD4-6 act as two independent units.
Michael Zaccak, Zena Qasem, Lada Gevorkyan-Airapetov, Sharon Ruthstein

2484 related Products with: An EPR Study on the Interaction between the Cu(I) Metal Binding Domains of ATP7B and the Atox1 Metallochaperone.

100.00 ul100.00 ul1 ml0.1 mg

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#32718272   // To Up

Melatonin-induced suppression of DNA methylation promotes odontogenic differentiation in human dental pulp cells.

Differentiation potency of human dental pulp cells (hDPCs) is essential for dentin regeneration. DNA methylation is one of the major epigenetic mechanisms and is suggested to involve in differentiation of hDPCs, the machinery of which includes DNA methyltransferase enzymes (DNMTs) and methyl-CpG-binding domain proteins (MBDs). Our previous study has found that melatonin (MT) promoted hDPC differentiation, but its mechanism remains elusive. We aimed to investigate the role of DNA methylation in the promotion of MT to differentiation of hDPCs . hDPCs were cultured in basal growth medium (CO) or odontogenic medium (OM) exposed to MT at different concentrations (0, 10, 10, 10, 10, 10 M). The cell growth was analyzed using Cell Counting Kit-8 assay, and mineralized tissue formation was measured using Alizarin red staining. The expression of the 10 genes () was determined using real-time qPCR and western blotting. The abundance of MeCP2 in the nuclei was evaluated using immunofluorescence analysis. Global methylation level was tested using ELISA. We found that mineralized tissue formation significantly increased in OM with MT at 10 M, while the levels of MeCP2 and global DNA methylation level declined. The expression of MBD1, MBD3, and MBD4 significantly increased in OM alone, and the expession of DNMT1 and MBD2 was decreased. These results indicate that MT promotes odontogenic differentiation of hDPCs by regulating the levels of DNMT1, MeCP2, and global DNA methylation, suggesting that MT-induced DNA methylation machinery may play an important role in tooth regeneration.
Jingzhou Li, Qianyi Deng, Wenguo Fan, Qi Zeng, Hongwen He, Fang Huang

2194 related Products with: Melatonin-induced suppression of DNA methylation promotes odontogenic differentiation in human dental pulp cells.

5 x 50 ug1.00 flask 100ul5ug1.00 flask50 ug1.00 flask50 ul1 mg1.00 flask100 ul10 ug

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#32517823   2020/06/10 To Up

Effects of feeding of vitamin C on post-hatch performance, immune status and DNA methylation-related gene expression in broiler chickens.

This study aimed to evaluate the effect of in ovo feeding (IOF) of vitamin C at embryonic age 11 (E11) on post-hatch performance, immune status and DNA methylation-related gene expression in broiler chickens. A total of 240 Arbor Acres breeder eggs (63 (sem 0·5) g) were randomly divided into two groups: normal saline and vitamin C (VC) groups. After incubation, newly hatched chicks from each group were randomly divided into six replicates with ten chicks per replicate. Hatchability, average daily feed intake (D21-42 and D1-42), and average daily gain and feed conversion ratio (D1-21) were improved by vitamin C treatment (P < 0·05). IOF of vitamin C increased vitamin C content (D1), total antioxidant capacity (D42), IgA (D1), IgM (D1 and D21), stimulation index for T lymphocyte (D35) and lysozyme activity (D21) in plasma (P < 0·05). On D21, vitamin C increased the splenic expression of IL-4 and DNMT1 and decreased IL-1β, Tet2, Tet3 and Gadd45β expression (P < 0·05). On D42, vitamin C increased the splenic expression of IL-4 and DNMT3A and decreased IFN-γ, Tet3, MBD4 and TDG expression (P < 0·05). In conclusion, the vitamin C via in ovo injection can be absorbed by broiler's embryo and IOF of vitamin C at E11 improves the post-hatch performance and immune status and, to some extent, the antioxidant capacity of broiler chickens. The expression of enzyme-related DNA methylation and demethylation indicates that the level of DNA methylation may increase in spleen in the VC group and whether the fluctuating expression of pro- and anti-inflammatory cytokines is related to DNA methylation change remained to be further investigated.
Yufei Zhu, Shizhao Li, Yulan Duan, Zhouzheng Ren, Xin Yang, Xiaojun Yang

2620 related Products with: Effects of feeding of vitamin C on post-hatch performance, immune status and DNA methylation-related gene expression in broiler chickens.

300 units2 Pieces/Box2 Pieces/Box2 Pieces/Box5 μg42 Pieces/Box100 ug42 Pieces/Box

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#32421892   2020/06/01 To Up

Germline loss-of-function variants in MBD4 are rare in Finnish patients with uveal melanoma.

Uveal melanoma (UM) is a rare intraocular cancer with the highest incidence in northern latitudes. Metastases develop in approximately 50% of patients, whereafter the median survival is 13 months. Generally, the mutation burden of these tumors is low. Germline variants predisposing to UM have been previously described in BRCA1-associated protein 1 (BAP1). Recently, germline and somatic loss-of-function (LOF) variants in the methyl-CpG-binding domain 4 (MBD4) gene have been found to cause a hypermutated UM, and MBD4 also has been put forward as a gene predisposing to UM. We sequenced for MBD4 germline variants in 440 Finnish patients with UM and identified seven rare exonic missense variants in 16 (3.6%) patients, of which one likely alters MBD4 function. The frequency of likely pathogenic variants in our cohort is 0.23% (1/432; 95% CI, 0.01-1.28). We identified no LOF variants though their frequency in the Finnish population is 0.052%. Thus, our data do not support the suggestion that MBD4 germline variants predispose to UM. Somatic loss of MBD4 might modify the mutational burden in UM and change its response to immune checkpoint inhibitors.
Pauliina Repo, Johannes E Jäntti, Reetta-Stiina Järvinen, Elina S Rantala, Martin Täll, Virpi Raivio, Tero T Kivelä, Joni A Turunen

1705 related Products with: Germline loss-of-function variants in MBD4 are rare in Finnish patients with uveal melanoma.

100 μg100ugcase

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#32415113   2020/05/15 To Up

Whole genome landscapes of uveal melanoma show an ultraviolet radiation signature in iris tumours.

Uveal melanoma (UM) is the most common intraocular tumour in adults and despite surgical or radiation treatment of primary tumours, ~50% of patients progress to metastatic disease. Therapeutic options for metastatic UM are limited, with clinical trials having little impact. Here we perform whole-genome sequencing (WGS) of 103 UM from all sites of the uveal tract (choroid, ciliary body, iris). While most UM have low tumour mutation burden (TMB), two subsets with high TMB are seen; one driven by germline MBD4 mutation, and another by ultraviolet radiation (UVR) exposure, which is restricted to iris UM. All but one tumour have a known UM driver gene mutation (GNAQ, GNA11, BAP1, PLCB4, CYSLTR2, SF3B1, EIF1AX). We identify three other significantly mutated genes (TP53, RPL5 and CENPE).
Peter A Johansson, Kelly Brooks, Felicity Newell, Jane M Palmer, James S Wilmott, Antonia L Pritchard, Natasa Broit, Scott Wood, Matteo S Carlino, Conrad Leonard, Lambros T Koufariotis, Vaishnavi Nathan, Aaron B Beasley, Madeleine Howlie, Rebecca Dawson, Helen Rizos, Chris W Schmidt, Georgina V Long, Hayley Hamilton, Jens F Kiilgaard, Timothy Isaacs, Elin S Gray, Olivia J Rolfe, John J Park, Andrew Stark, Graham J Mann, Richard A Scolyer, John V Pearson, Nicolas van Baren, Nicola Waddell, Karin W Wadt, Lindsay A McGrath, Sunil K Warrier, William Glasson, Nicholas K Hayward

1298 related Products with: Whole genome landscapes of uveal melanoma show an ultraviolet radiation signature in iris tumours.

50 UG100 μg100 μg100 μg100 μg

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#32383112   // To Up

Kinetic Milestones of Damage Recognition by DNA Glycosylases of the Helix-Hairpin-Helix Structural Superfamily.

X-ray data show that DNA glycosylases, which initiate the pathway of base excision repair in DNA, belong to six structural superfamilies. Here, we provide an overview of the latest results of kinetic studies on the mechanisms of specific recognition of a damaged nucleotide at the early steps of DNA repair by human (OGG1 and MBD4) or Escherichia coli (Nth and MutY) N-DNA-glycosylases belonging to superfamily Helix-hairpin-Helix (HhH). A comparison of real-time conformational transformations of DNA glycosylases and DNA with the structural data obtained for free enzymes and their complexes with substrates and intermediates have made it possible to build molecular-kinetic models of the enzymatic processes. These models have allowed researchers to associate the conformational transitions of the interacting molecules with elementary steps of an enzymatic process. Additionally, these models have revealed the stages that make the largest contribution to the specificity of the enzyme for DNA substrates. These data provide an opportunity to gain further insight into the structural and dynamic principles underlying the enzymatic processes that ensure highly efficient functioning of the repair-protective system of all living organisms and that maintain DNA integrity.
Nikita A Kuznetsov, Olga S Fedorova

1558 related Products with: Kinetic Milestones of Damage Recognition by DNA Glycosylases of the Helix-Hairpin-Helix Structural Superfamily.

5 G50 umoles10240/kit100.00 ul 100 G50ul (1mg/ml)5100 ug/vial500IU100ug

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