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Demethylase

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https://www.readbyqxmd.com/read/29144447/bcat1-restricts-%C3%AE-kg-levels-in-aml-stem-cells-leading-to-idhmut-like-dna-hypermethylation
#1
Simon Raffel, Mattia Falcone, Niclas Kneisel, Jenny Hansson, Wei Wang, Christoph Lutz, Lars Bullinger, Gernot Poschet, Yannic Nonnenmacher, Andrea Barnert, Carsten Bahr, Petra Zeisberger, Adriana Przybylla, Markus Sohn, Martje Tönjes, Ayelet Erez, Lital Adler, Patrizia Jensen, Claudia Scholl, Stefan Fröhling, Sibylle Cocciardi, Patrick Wuchter, Christian Thiede, Anne Flörcken, Jörg Westermann, Gerhard Ehninger, Peter Lichter, Karsten Hiller, Rüdiger Hell, Carl Herrmann, Anthony D Ho, Jeroen Krijgsveld, Bernhard Radlwimmer, Andreas Trumpp
The branched-chain amino acid (BCAA) pathway and high levels of BCAA transaminase 1 (BCAT1) have recently been associated with aggressiveness in several cancer entities. However, the mechanistic role of BCAT1 in this process remains largely uncertain. Here, by performing high-resolution proteomic analysis of human acute myeloid leukaemia (AML) stem-cell and non-stem-cell populations, we find the BCAA pathway enriched and BCAT1 protein and transcripts overexpressed in leukaemia stem cells. We show that BCAT1, which transfers α-amino groups from BCAAs to α-ketoglutarate (αKG), is a critical regulator of intracellular αKG homeostasis...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29142071/chromatin-histone-modifications-and-rigidity-affect-nuclear-morphology-independent-of-lamins
#2
Andrew D Stephens, Patrick Z Liu, Edward J Banigan, Luay M Almassalha, Vadim Backman, Stephen A Adam, Robert D Goldman, John F Marko
Nuclear shape and architecture influence gene localization, mechanotransduction, transcription, and cell function. Abnormal nuclear morphology and protrusions termed "blebs" are diagnostic markers for many human afflictions including heart disease, aging, progeria, and cancer. Nuclear blebs are associated with both lamin and chromatin alterations. A number of prior studies suggest that lamins dictate nuclear morphology, but the contributions of altered chromatin compaction remain unclear. We show that chromatin histone modification state dictates nuclear rigidity, and modulating it is sufficient to both induce and suppress nuclear blebs...
November 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29140109/host-methyltransferases-and-demethylases-potential-new-epigenetic-targets-for-hiv-cure-strategies-and-beyond
#3
Daniela Boehm, Melanie Ott
A successful HIV cure strategy may require reversing HIV latency to purge hidden viral reservoirs or enhancing HIV latency to permanently silence HIV transcription. Epigenetic modifying agents show promise as antilatency therapeutics in vitro and ex vivo, but also affect other steps in the viral life cycle. In this review, we summarize what we know about cellular DNA and protein methyltransferases (PMTs) as well as demethylases involved in HIV infection. We describe the biology and function of DNA methyltransferases, and their controversial role in HIV infection...
November 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29137219/functional-characterization-of-lysine-specific-demethylase-2-lsd2-kdm1b-in-breast-cancer-progression
#4
Lin Chen, Shauna N Vasilatos, Ye Qin, Tiffany A Katz, Chunyu Cao, Hao Wu, Nilgun Tasdemir, Kevin M Levine, Steffi Oesterreich, Nancy E Davidson, Yi Huang
Flavin-dependent histone demethylases govern histone H3K4 methylation and act as important chromatin modulators that are extensively involved in regulation of DNA replication, gene transcription, DNA repair, and heterochromatin gene silencing. While the activities of lysine-specific demethylase 1 (LSD1/KDM1A) in facilitating breast cancer progression have been well characterized, the roles of its homolog LSD2 (KDM1B) in breast oncogenesis are relatively less understood. In this study, we showed that LSD2 protein level was significantly elevated in malignant breast cell lines compared with normal breast epithelial cell line...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136510/genomic-subtypes-of-non-invasive-bladder-cancer-with-distinct-metabolic-profile-and-female-gender-bias-in-kdm6a-mutation-frequency
#5
Carolyn D Hurst, Olivia Alder, Fiona M Platt, Alastair Droop, Lucy F Stead, Julie E Burns, George J Burghel, Sunjay Jain, Leszek J Klimczak, Helen Lindsay, Jo-An Roulson, Claire F Taylor, Helene Thygesen, Angus J Cameron, Anne J Ridley, Helen R Mott, Dmitry A Gordenin, Margaret A Knowles
Bladder cancer incurs a higher lifetime treatment cost than other cancers due to frequent recurrence of non-invasive disease. Improved prognostic biomarkers and localized therapy are needed for this large patient group. We defined two major genomic subtypes of primary stage Ta tumors. One of these was characterized by loss of 9q including TSC1, increased KI67 labeling index, upregulated glycolysis, DNA repair, mTORC1 signaling, features of the unfolded protein response, and altered cholesterol homeostasis. Comparison with muscle-invasive bladder cancer mutation profiles revealed lower overall mutation rates and more frequent mutations in RHOB and chromatin modifier genes...
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29134244/modulation-of-cyp3a-enzyme-activity-by-diosmin-and-its-consequence-on-carbamazepine-pharmacokinetics-in-rats
#6
Satish Kumar Bedada, Prasad Neerati
Diosmin is a widely used flavonoid for the treatment of varicose veins and hemorrhoids. Epileptic patients with hemorrhoids and varicose veins may use diosmin along with carbamazepine (CBZ) therapy, which leads to pharmacokinetic interaction between diosmin and CBZ. Therefore, the present study was performed to evaluate the effect of diosmin on the pharmacokinetics of CBZ in rats. Diosmin-mediated altered CYP3A enzyme activity in human and rat liver microsomes was examined using CYP3A dependent erythromycin N-demethylase assay...
November 14, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29126261/heme-promotes-transcriptional-and-demethylase-activities-of-gis1-a-member-of-the-histone-demethylase-jmjd2-kdm4-family
#7
Sneha Lal, Jonathan M Comer, Purna C Konduri, Ajit Shah, Tianyuan Wang, Anthony Lewis, Grant Shoffner, Feng Guo, Li Zhang
The yeast Gis1 protein is a transcriptional regulator belonging to the JMJD2/KDM4 subfamily of demethylases that contain a JmjC domain, which are highly conserved from yeast to humans. They have important functions in histone methylation, cellular signaling and tumorigenesis. Besides serving as a cofactor in many proteins, heme is known to directly regulate the activities of proteins ranging from transcriptional regulators to potassium channels. Here, we report a novel mechanism governing heme regulation of Gis1 transcriptional and histone demethylase activities...
November 6, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29122178/pdslt2-penicillium-digitatum-mitogen-activated-protein-kinase-controls-sporulation-and-virulence-during-citrus-fruit-infection
#8
Marta de Ramón-Carbonell, Paloma Sánchez-Torres
The Slt2 mitogen-activated protein (MAP) kinase homologue of Penicillium digitatum, the most relevant pathogen-producing citrus green mould decay during postharvest, was identified and explored. The P. digitatum Slt2-MAPK coding gene (PdSlt2) was functionally characterized by homologous gene elimination and transcriptomic evaluation. The absence of PdSlt2 gene resulted in significantly reduced virulence during citrus infection. The ΔPdSlt2 mutants were also defective in asexual reproduction, showing impairment of sporulation during citrus infection...
December 2017: Fungal Biology
https://www.readbyqxmd.com/read/29115523/characterization-of-cholesterol-metabolism-in-sertoli-cells-and-spermatogenesis-review
#9
Jin-Feng Shi, Yu-Kun Li, Kun Ren, Yuan-Jie Xie, Wei-Dong Yin, Zhong-Cheng Mo
The Sertoli cell, which is the supporting cell of spermatogenesis, has an important role in the endocrine and paracrine control of spermatogenesis. Functionally, it provides the cells of the seminiferous epithelium with nutrition, conveys mature spermatids to the lumen of seminiferous tubules, secretes androgen‑binding protein and interacts with endocrine Leydig cells. In addition, the levels of cholesterol, as well as its intermediates, vary greatly between nongonadal tissues and the male reproductive system...
November 7, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29113308/kdm4a-as-a-prognostic-marker-of-oral-squamous-cell-carcinoma-evidence-from-tissue-microarray-studies-in-a-multicenter-cohort
#10
Xin Jin, Hao Xu, Xingyu Wu, Taiwen Li, Jing Li, Yu Zhou, Hongxia Dan, Lu Jiang, Xin Zeng, Ping Ji, Qianming Chen
Purpose: Previous studies have identified histone demethylase KDM4A to be a key epigenetic priming factor for the invasive squamous cell carcinoma growth and metastasis. The purpose of this study was to examine KDM4A as an independent prognostic marker in oral squamous cell carcinoma, using multicenter tissue microarrays. Results: The expression of KDM4A was significantly correlated with lymph node metastasis and TNM stage. KDM4A overexpression was associated with poor overall survival, and it was found to be a statistically significant independent predictor of all-cause mortality...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29112162/syntheses-of-novel-4-substituted-n-5-amino-1h-1-2-4-triazol-3-yl-pyridine-3-sulfonamide-derivatives-with-potential-antifungal-activity
#11
Krzysztof Szafrański, Jarosław Sławiński, Anna Kędzia, Ewa Kwapisz
Candidiasis represent a serious threat for patients with altered immune responses. Therefore, we have undertaken the synthesis of compounds comprising a pyridine-3-sulfonamide scaffold and known antifungally active 1,2,4-triazole substituents. Thus a series of novel 4-substituted N-(5-amino-1H-1,2,4-triazol-3-yl)pyridine-3-sulfonamides have been synthesized by multistep reactions starting from 4-chloropyridine-3-sulfonamide via N'-cyano-N-[(4-substitutedpyridin-3-yl)sulfonyl]carbamimidothioates which were further converted with hydrazine hydrate to the corresponding 1,2,4-triazole derivatives 26-36...
November 7, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29111428/kdm6-and-kdm4-histone-lysine-demethylases-emerge-as-molecular-therapeutic-targets-in-human-acute-myeloid-leukemia
#12
Liberalis Debraj Boila, Shankha Subhra Chatterjee, Debasis Banerjee, Amitava Sengupta
Acute myeloid leukemia (AML) remains an aggressive hematopoietic malignancy caused by proliferation of immature myeloid cells, which is frequently characterized by perturbations in chromatin modifying enzymes. Emerging evidences indicate that histone demethylases play instructive role in tumorigenesis. However, due to the complexity of this enormous family of histone-modifying enzymes, substrate redundancy and context-specific roles, the contribution of each member remains ambiguous and targeting them remains challenging...
October 27, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/29108280/trimethylation-of-h3k27-during-human-cerebellar-development-in-relation-to-medulloblastoma
#13
Shahryar E Mir, Michiel Smits, Dennis Biesmans, Machteld Julsing, Marianna Bugiani, Eleonora Aronica, Gertjan J L Kaspers, Jacqueline Cloos, Thomas Würdinger, Esther Hulleman
Medulloblastoma (MB), the most common malignant childhood brain tumor, encompasses a collection of four clinically and molecularly distinct tumor subgroups, i.e. WNT, SHH, Group 3 and Group 4. These tumors are believed to originate from precursor cells during cerebellar development. Although the exact etiology of these brain tumors is not yet known, histone modifications are increasingly recognized as key events during cerebellum development and MB tumorigenesis. Recent studies show that key components involved in post-translational modifications of histone H3 lysine 27 (H3K27) are commonly deregulated in MB...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29107372/hepatotoxicity-of-paraquat-on-common-carp-cyprinus-carpio-l
#14
Junguo Ma, Yuanyuan Li, Weiguo Li, Xiaoyu Li
Paraquat (PQ) is a nonselective herbicide that is used worldwide and has been demonstrated to be a high risk to aquatic organisms. However, relatively little is known about the mechanisms on detoxification and hepatotoxicity of PQ in fish. In the present study, a sub-acute toxicity test of PQ exposure on common carp at 1.596 and 3.192mgL(-1) for 7d was conducted under laboratory conditions. The results showed that the transcriptional levels of cytochrome P450s (CYPs), such as CYP1A, CYP2K, and CYP3A138, GSTα and GSTpi, and export pump gene MDR1, as well as the erythromycin-N-demethylase (ERND) activity were generally up-regulated by PQ exposure for 7d, indicating that these genes or enzymes are potentially involved in the detoxification of PQ in the fish liver...
October 26, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/29105293/a-new-mechanism-for-reduced-sensitivity-to-demethylation-inhibitor-fungicides-in-the-fungal-banana-black-sigatoka-pathogen-pseudocercospora-fijiensis
#15
Caucasella Diaz-Trujillo, Pablo Chong, Ioannis Stergiopoulos, Viviane Cordovez, Mauricio Guzman, Pierre J G M De Wit, Harold J G Meijer, Rafael E Arango Isaza, Gabriel Scalliet, Helge Sierotzki, Esther Lilia Peralta, Gerrit H J Kema
The Dothideomycete Pseudocercospora fijiensis, previously Mycosphaerella fijiensis, is the causal agent of black Sigatoka, one of the most destructive diseases of bananas and plantains. Disease management depends on fungicide applications with a major share for sterol demethylation-inhibitors (DMIs). The continued use of DMIs puts a considerable selection pressure on natural P. fijiensis populations enabling the selection of novel genotypes with reduced sensitivity. The hitherto explanatory mechanism for this reduced sensitivity was the presence of non-synonymous point mutations in the target gene Pfcyp51, encoding the sterol 14α-demethylase enzyme...
November 4, 2017: Molecular Plant Pathology
https://www.readbyqxmd.com/read/29104258/epigenetic-regulatory-mechanisms-induced-by-resveratrol
#16
REVIEW
Guilherme Felipe Santos Fernandes, Gabriel Dalio Bernardes Silva, Aline Renata Pavan, Diego Eidy Chiba, Chung Man Chin, Jean Leandro Dos Santos
Resveratrol (RVT) is one of the main natural compounds studied worldwide due to its potential therapeutic use in the treatment of many diseases, including cancer, diabetes, cardiovascular diseases, neurodegenerative diseases and metabolic disorders. Nevertheless, the mechanism of action of RVT in all of these conditions is not completely understood, as it can modify not only biochemical pathways but also epigenetic mechanisms. In this paper, we analyze the biological activities exhibited by RVT with a focus on the epigenetic mechanisms, especially those related to DNA methyltransferase (DNMT), histone deacetylase (HDAC) and lysine-specific demethylase-1 (LSD1)...
November 1, 2017: Nutrients
https://www.readbyqxmd.com/read/29101321/contribution-of-epigenetic-landscapes-and-transcription-factors-to-x-chromosome-reactivation-in-the-inner-cell-mass
#17
Maud Borensztein, Ikuhiro Okamoto, Laurène Syx, Guillaume Guilbaud, Christel Picard, Katia Ancelin, Rafael Galupa, Patricia Diabangouaya, Nicolas Servant, Emmanuel Barillot, Azim Surani, Mitinori Saitou, Chong-Jian Chen, Konstantinos Anastassiadis, Edith Heard
X-chromosome inactivation is established during early development. In mice, transcriptional repression of the paternal X-chromosome (Xp) and enrichment in epigenetic marks such as H3K27me3 is achieved by the early blastocyst stage. X-chromosome inactivation is then reversed in the inner cell mass. The mechanisms underlying Xp reactivation remain enigmatic. Using in vivo single-cell approaches (allele-specific RNAseq, nascent RNA-fluorescent in situ hybridization and immunofluorescence), we show here that different genes are reactivated at different stages, with more slowly reactivated genes tending to be enriched in H3meK27...
November 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/29099285/critical-roles-of-protein-methyltransferases-and-demethylases-in-the-regulation-of-embryonic-stem-cell-fate
#18
Theodore Vougiouklakis, Yusuke Nakamura, Vassiliki Saloura
Accumulating evidence has recently shown that protein methyltransferases and demethylases are crucial regulators in either maintaining pluripotent states or inducing differentiation of embryonic stem cells. These enzymes control pluripotent signatures by mediating activation or repression of histone marks, or through direct methylation of non-histone proteins. Importantly, chromatin modifiers can influence the fate of many differentiation-related genes by loosening chromatin and allowing for transcriptional activation of lineage-specific genes...
November 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29099276/setdb2-and-riox2-are-differentially-expressed-among-renal-cell-tumor-subtypes-associating-with-prognosis-and-metastization
#19
Maria João Ferreira, Ana Sílvia Pires-Luís, Márcia Vieira-Coimbra, Pedro Costa-Pinheiro, Luís Antunes, Paula C Dias, Francisco Lobo, Jorge Oliveira, Céline S Gonçalves, Bruno M Costa, Rui Henrique, Carmen Jerónimo
Increasing detection of small renal masses by imaging techniques entails the need for accurate discrimination between benign and malignant renal cell tumors (RCTs) as well as among malignant RCTs, owing to differential risk of progression through metastization. Although histone methylation has been implicated in renal tumorigenesis, its potential as biomarker for renal cell carcinoma (RCC) progression remains largely unexplored. Thus, we aimed to characterize the differential expression of histone methyltransferases (HMTs) and histone demethylases (HDMs) in RCTs to assess their potential as metastasis biomarkers...
November 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29097205/characterization-of-human-alkb-homolog-1-produced-in-mammalian-cells-and-demonstration-of-mitochondrial-dysfunction-in-alkbh1-deficient-cells
#20
Tina A Müller, Sarah L Struble, Katheryn Meek, Robert P Hausinger
Alkbh1 is a mammalian homolog of the Escherichia coli DNA repair enzyme AlkB, an Fe(II) and 2-oxoglutarate dependent dioxygenase that removes alkyl lesions from DNA bases. The human homolog ALKBH1 has been associated with six different enzymatic activities including DNA or tRNA hydroxylation, cleavage at abasic (AP) sites in DNA, as well as demethylation of histones. The reported cellular roles of this protein reflect the diverse enzymatic activities and include direct DNA repair, tRNA modification, and histone modification...
October 30, 2017: Biochemical and Biophysical Research Communications
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