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https://www.readbyqxmd.com/read/30515476/identification-of-deregulated-signaling-pathways-in-jurkat-cells-in-response-to-a-novel-acylspermidine-analogue-n-4-erucoyl-spermidine
#1
Syed Shoeb Razvi, Hani Choudhry, Mohammed Nihal Hasan, Mohammed A Hassan, Said Salama Moselhy, Khalid Omer Abualnaja, Mazin A Zamzami, Taha Abduallah Kumosani, Abdulrahman Labeed Al-Malki, Majed A Halwani, Abdulkhaleg Ibrahim, Ali Hamiche, Christian Bronner, Tadao Asami, Mahmoud Alhosin
Natural polyamines such as putrescine, spermidine, and spermine are crucial in the cell proliferation and maintenance in all the eukaryotes. However, the requirement of polyamines in tumor cells is stepped up to maintain tumorigenicity. Many synthetic polyamine analogues have been designed recently to target the polyamine metabolism in tumors to induce apoptosis. N4 -Erucoyl spermidine (designed as N4 -Eru), a novel acylspermidine derivative, has been shown to exert selective inhibitory effects on both hematological and solid tumors, but its mechanisms of action are unknown...
2018: Epigenetics insights
https://www.readbyqxmd.com/read/30458291/the-kdm-kmt-gene-families-in-the-self-fertilizing-mangrove-rivulus-fish-kryptolebias-marmoratus-suggest-involvement-of-histone-methylation-machinery-in-development-and-reproduction
#2
Alexandre Fellous, Ryan L Earley, Frederic Silvestre
Histone modifications such as methylation of key lysine residues play an important role in embryonic development in a variety of organisms such as of Pacific oysters, zebrafish and mice. The action of demethylase ("erasers") and methyltransferase ("writers") enzymes regulates precisely the methylation status of each lysine residue. However, despite fishes being very useful model organisms in medicine, evolution and ecotoxicology, most studies have focused on mammalian and plant model organisms, and mechanisms underlying regulation of histones are unknown in fish development outside of zebrafish...
November 17, 2018: Gene
https://www.readbyqxmd.com/read/30444719/inhibition-of-rna-synthesis-during-scriptaid-exposure-enhances-gene-reprogramming-in-scnt-embryos
#3
Vitor B Rissi, Werner Giehl Glanzner, Mariana Priotto de Macedo, Lady Katerine Serrano Mujica, Karine Campagnolo, Karina Gutierrez, Alessandra Bridi, Hernan Baldassarre, Paulo Bayard Gonçalves, Vilceu Bordignon
Insufficient epigenetic reprogramming is incompatible with normal development of embryos produced by somatic cell nuclear transfer (SCNT), but treatment with histone deacetylases inhibitors (HDACi) enhance development of SCNT embryos. However, the mechanisms underpinning HDACi benefits in SCNT embryos remain largely uncharacterized. We hypothesized that, in addition to enhancing reprogramming, HDACi treatment may promote expression of genes not required for early development of SCNT embryos. To test this hypothesis, RNA synthesis was inhibited by treating bovine SCNT embryos with 5,6-Dichlorobenzimidazole 1-β-D-ribofuranoside (DBR), which were concomitantly treated or not with Scriptaid (Scrip; an HDACi)...
November 1, 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/30426231/unraveling-kdm4-histone-demethylase-expression-and-its-association-with-adverse-cytogenetic-findings-in-chronic-lymphocytic-leukemia
#4
Luma Dayane de Carvalho Filiú-Braga, Teresa Raquel Tavares Serejo, Antonio Roberto Lucena-Araujo, Francisco Assis Rocha Neves, Juliana Lott de Carvalho, Eduardo Magalhaes Rego, Felipe Saldanha-Araujo
The acquisition of complex karyotypes is related to the progression of chronic lymphocytic leukemia (CLL) and patients with this condition have a poor prognosis. Despite recent advances in the classification of prognosis in CLL patients, understanding of the molecular mechanisms that lead to genomic instability and progression of this disease remains inadequate. Interestingly, dysregulated expression of KDM4 members is involved in the progression of several cancer types and plays a role in the DNA damage response; however, the gene expression profile and the importance of KDM4 members in CLL are still unknown...
November 13, 2018: Medical Oncology
https://www.readbyqxmd.com/read/30358834/genome-wide-differential-methylation-analyses-identifies-methylation-signatures-of-male-infertility
#5
Kumar Mohanty Sujit, Saumya Sarkar, Vertika Singh, Rajesh Pandey, Neeraj Kumar Agrawal, Sameer Trivedi, Kiran Singh, Gopal Gupta, Singh Rajender
STUDY QUESTION: Do methylation changes in sperm DNA correlate with infertility? STUDY ANSWER: Loss of spermatogenesis and fertility was correlated with 1680 differentially-methylated CpGs (DMCs) across 1052 genes. WHAT IS KNOWN ALREADY: Methylation changes in a number of genes have been correlated with reduced sperm count and motility. STUDY DESIGN, SIZE, DURATION: This case-control study used spermatozoal DNA from 38 oligo-/oligoastheno-zoospermic infertile patients and 26 normozoospermic fertile men...
December 1, 2018: Human Reproduction
https://www.readbyqxmd.com/read/30132131/genetic-alterations-of-9p24-in-lymphomas-and-their-impact-for-cancer-immuno-therapy
#6
Thomas Menter, Alexandar Tzankov
Chromosome 9 harbors several relevant oncogenes related to hematolymphoid malignancies and one specific region, 9p24, has come into the focus of attention in the last years as it contains recurrently mutant genes of therapeutic interest. The most prominent genes of this locus are programmed death ligands 1 and 2 (PDL1/PDL2), with the amplification of PDL1 being a hallmark of both classical Hodgkin and primary mediastinal B cell lymphoma, and Janus kinase 2 (JAK2), which is point-mutated in myeloproliferative neoplasms and other myeloid malignancies, and rearranged in PCM1-JAK2-positive myeloid/lymphoid neoplasms with eosinophila...
August 21, 2018: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/30083054/kdm4c-is-recruited-to-mitotic-chromosomes-and-is-relevant-for-chromosomal-stability-cell-migration-and-invasion-of-triple-negative-breast-cancer-cells
#7
Jeison Garcia, Fernando Lizcano
Members of the jumonji-containing lysine demethylase protein family have been associated with cancer development, although their specific roles in the evolution of tumor cells remain unknown. This work examines the effects of lysine demethylase 4C (KDM4C) knockdown on the behavior of a triple-negative breast cancer cell line. KDM4C expression was knocked-down by siRNA and analyzed by Western blot and immunofluorescence. HCC38 cell proliferation was examined by MTT assay, while breast cancer cells' migration and invasion were tested in Transwell format by chemotaxis...
2018: Breast Cancer: Basic and Clinical Research
https://www.readbyqxmd.com/read/29759937/identification-of-epigenetic-regulators-of-dux4-fl-for-targeted-therapy-of-facioscapulohumeral-muscular-dystrophy
#8
Charis L Himeda, Takako I Jones, Ching-Man Virbasius, Lihua Julie Zhu, Michael R Green, Peter L Jones
Facioscapulohumeral muscular dystrophy (FSHD) is caused by epigenetic de-repression of the disease locus, leading to pathogenic misexpression of the DUX4 gene in skeletal muscle. While the factors and pathways involved in normal repression of the FSHD locus in healthy cells have been well characterized, very little is known about those responsible for the aberrant activation of DUX4-fl in FSHD myocytes. Reasoning that DUX4-fl activators might represent useful targets for small molecule inhibition, we performed a highly targeted, candidate-based screen of epigenetic regulators in primary FSHD myocytes...
July 5, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29748339/correction-cross-phenotype-analysis-of-immunochip-data-identifies-kdm4c-as-a-relevant-locus-for-the-development-of-systemic-vasculitis
#9
(no author information available yet)
No abstract text is available yet for this article.
June 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29718303/the-kdm4a-kdm4c-nf-%C3%AE%C2%BAb-and-wdr5-epigenetic-cascade-regulates-the-activation-of-b-cells
#10
Kuo-Hsuan Hung, Yong H Woo, I-Ying Lin, Chin-Hsiu Liu, Li-Chieh Wang, Hsin-Yu Chen, Bor-Luen Chiang, Kuo-I Lin
T follicular helper (Tfh) cell-derived signals promote activation and proliferation of antigen-primed B cells. It remains unclear whether epigenetic regulation is involved in the B cell responses to Tfh cell-derived signals. Here, we demonstrate that Tfh cell-mimicking signals induce the expression of histone demethylases KDM4A and KDM4C, and the concomitant global down-regulation of their substrates, H3K9me3/me2, in B cells. Depletion of KDM4A and KDM4C potentiates B cell activation and proliferation in response to Tfh cell-derived signals...
June 20, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29682190/the-jmjn-domain-as-a-dimerization-interface-and-a-targeted-inhibitor-of-kdm4-demethylase-activity
#11
May Levin, Michal Stark, Yehuda G Assaraf
Histone methylation is regulated to shape the epigenome by modulating DNA compaction, thus playing central roles in fundamental chromatin-based processes including transcriptional regulation, DNA repair and cell proliferation. Histone methylation is erased by demethylases including the well-established KDM4 subfamily members, however, little is known about their dimerization capacity and its impact on their demethylase activity. Using the powerful bimolecular fluorescence complementation technique, we herein show the in situ formation of human KDM4A and KDM4C homodimers and heterodimers in nuclei of live transfectant cells and evaluate their H3K9me3 demethylation activity...
March 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29528362/histone-3-lysine-4-9-and-27-demethylases-expression-profile-in-fertilized-and-cloned-bovine-and-porcine-embryos
#12
Werner Giehl Glanzner, Vitor Braga Rissi, Mariana Priotto de Macedo, Lady Katerine Serrano Mujica, Karina Gutierrez, Alessandra Bridi, João Ricardo Malheiros de Souza, Paulo Bayard Dias Gonçalves, Vilceu Bordignon
Epigenetic modifications in the C-terminal domain of histones coordinate important events during early development including embryo genome activation (EGA) and cell differentiation. In this study, the mRNA expression profile of the main lysine demethylases (KDMs) acting on the lysine 4 (H3K4), 9 (H3K9), and 27 (H3K27) of the histone H3 was determined at pre-, during and post-EGA stages of bovine and porcine embryos produced by in vitro fertilization (IVF) and somatic cell nuclear transfer (SCNT). In IVF embryos, mRNA abundance of most KDMs revealed a bell-shaped profile with peak expression around the EGA period, i...
June 1, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29402611/structure-activity-studies-of-a-macrocyclic-peptide-inhibitor-of-histone-lysine-demethylase-4a
#13
Toby Passioura, Bhaskar Bhushan, Anthony Tumber, Akane Kawamura, Hiroaki Suga
The combination of genetic code reprogramming and mRNA display is a powerful approach for the identification of macrocyclic peptides with high affinities to a target of interest. We have previously used such an approach to identify a potent inhibitor (CP2) of the human KDM4A and KDM4C lysine demethylases; important regulators of gene expression. In the present study, we have used genetic code reprogramming to synthesise very high diversity focused libraries (>1012 compounds) based on CP2 and, through affinity screening, used these to delineate the structure activity relationship of CP2 binding to KDM4A...
March 15, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29374629/cross-phenotype-analysis-of-immunochip-data-identifies-kdm4c-as-a-relevant-locus-for-the-development-of-systemic-vasculitis
#14
Lourdes Ortiz-Fernández, Francisco David Carmona, Raquel López-Mejías, Maria Francisca González-Escribano, Paul A Lyons, Ann W Morgan, Amr H Sawalha, Kenneth G C Smith, Miguel A González-Gay, Javier Martín
OBJETIVE: Systemic vasculitides represent a heterogeneous group of rare complex diseases of the blood vessels with a poorly understood aetiology. To investigate the shared genetic component underlying their predisposition, we performed the first cross-phenotype meta-analysis of genetic data from different clinically distinct patterns of vasculitis. METHODS: Immunochip genotyping data from 2465 patients diagnosed with giant cell arteritis, Takayasu's arteritis, antineutrophil cytoplasmic antibody-associated vasculitis or IgA vasculitis as well as 4632 unaffected controls were analysed to identify common susceptibility loci for vasculitis development...
April 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29339137/oxygen-induced-alterations-in-the-expression-of-chromatin-modifying-enzymes-and-the-transcriptional-regulation-of-imprinted-genes
#15
William M Skiles, Avery Kester, Jane H Pryor, Mark E Westhusin, Michael C Golding, Charles R Long
Embryo culture and assisted reproductive technologies have been associated with a disproportionately high number of epigenetic abnormalities in the resulting offspring. However, the mechanisms by which these techniques influence the epigenome remain poorly defined. In this study, we evaluated the capacity of oxygen concentration to influence the transcriptional control of a selection of key enzymes regulating chromatin structure. In mouse embryonic stem cells, oxygen concentrations modulated the transcriptional regulation of the TET family of enzymes, as well as the de novo methyltransferase Dnmt3a...
June 2018: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/28396876/reduced-histone-h3-lysine-9-methylation-contributes-to-the-pathogenesis-of-latent-autoimmune-diabetes-in-adults-via-regulation-of-suv39h2-and-kdm4c
#16
Xi-Yu Liu, Hong Li
Aims. Latent autoimmune diabetes in adults (LADA) is an autoimmune disease of which the mechanism is not clear. Emerging evidence suggests that histone methylation contributes to autoimmunity. Methods. Blood CD4(+) T lymphocytes from 26 LADA patients and 26 healthy controls were isolated to detect histone H3 lysine 4 and H3 lysine 9 methylation status. Results. Reduced global H3 lysine 9 methylation was observed in LADA patients' CD4(+) T lymphocytes, compared to healthy controls (P < 0.05). H3 lysine 4 methylation was not statistically different...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28236704/jumonji-domain-containing-2c-promotes-cell-migration-and-invasion-through-modulating-cul4a-expression-in-lung-cancer
#17
Na Li, Dazhi Jiang
Jumonji domain containing 2C (JMJD2C), also named as KDM4C, was found to a transcriptional cofactor and enzyme that catalyzes demethylation of histone H3 lysine 9 and 36. Here in this study, we found that the expression of JMJD2C increased in a majority of the human lung cancer tissues examined compared with adjacent tissues. Furthermore, the expression of JMJD2C was found to be higher in metastatic lung cancer tissues than which in non-metastatic lung cancer tissues. Knockdown of JMJD2C inhibited the ability of migration and invasion of lung cancer cells...
May 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27978997/corrigendum-to-kdm4c-a-h3k9me3-histone-demethylase-is-involved-in-the-maintenance-of-human-escc-initiating-cells-by-epigenetically-enhancing-sox2-expression-neoplasia-18-2016-594-609
#18
Xiang Yuan, Jinyu Kong, Zhikun Ma, Na Li, Ruinuo Jia, Yiwen Liu, Fuyou Zhou, Qimin Zhan, Gang Liu, Shegan Gao
No abstract text is available yet for this article.
December 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27840577/kdm4c-activity-modulates-cell-proliferation-and-chromosome-segregation-in-triple-negative-breast-cancer
#19
Jeison Garcia, Fernando Lizcano
The Jumonji-containing domain protein, KDM4C, is a histone demethylase associated with the development of several forms of human cancer. However, its specific function in the viability of tumoral lineages is yet to be determined. This work investigates the importance of KDM4C activity in cell proliferation and chromosome segregation of three triple-negative breast cancer cell lines using a specific demethylase inhibitor. Immunofluorescence assays show that KDM4C is recruited to mitotic chromosomes and that the modulation of its activity increases the number of mitotic segregation errors...
2016: Breast Cancer: Basic and Clinical Research
https://www.readbyqxmd.com/read/27742014/kdm4c-a-h3k9me3-histone-demethylase-is-involved-in-the-maintenance-of-human-escc-initiating-cells-by-epigenetically-enhancing-sox2-expression
#20
Xiang Yuan, Jinyu Kong, Zhikun Ma, Na Li, Ruinuo Jia, Yiwen Liu, Fuyou Zhou, Qimin Zhan, Gang Liu, Shegan Gao
Our studies investigating the existence of tumor-initiating cell (TIC) populations in human esophageal squamous cell carcinoma (ESCC) had identified a subpopulation of cells isolated from ESCC patient-derived tumor specimens marked by an ALDHbri+ phenotype bear stem cell-like features. Importantly, KDM4C, a histone demethylase was enhanced in ALDHbri+ subpopulation, suggesting that strategies interfering with KDM4C may be able to target these putative TICs. In the present study, by genetic and chemical means, we demonstrated that, KDM4C blockade selectively decreased the ESCC ALDHbri+ TICs population in vitro and specifically targeted the TICs in ALDHbri+ -derived xenograft, retarding engraftment...
October 2016: Neoplasia: An International Journal for Oncology Research
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