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https://www.readbyqxmd.com/read/27871311/erratum-to-jmjd2a-contributes-to-breast-cancer-progression-through-transcriptional-repression-of-the-tumor-suppressor-arhi
#1
Li-Liang Li, Ai-Min Xue, Bei-Xu Li, Yi-Wen Shen, Yu-Hua Li, Cheng-Liang Luo, Ming-Chang Zhang, Jie-Qing Jiang, Zu-De Xu, Jian-Hui Xie, Zi-Qin Zhao
No abstract text is available yet for this article.
November 21, 2016: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/27743893/lgr4-promotes-prostate-tumorigenesis-through-the-jmjd2a-ar-signaling-pathway
#2
Jianwei Zhang, Qi Li, Shaojin Zhang, Quanquan Xu, Tianen Wang
Lgr4 (leucine-rich repeat domain containing G protein-coupled receptor 4) is implicated in the transcriptional regulation of multiple histone demethylases in the progression of diverse cancers, but there are few reports concerning the molecular mechanism by which Lgr4 regulates histone demethylase activation in prostate cancer (PCa) progression. As Jmjd2a is a histone demethylase, in the current study, we investigated the relationship between interaction Lgr4 with Jmjd 2a and Jmjd2a/androgen receptor (AR) signaling pathway in PCa progression...
October 12, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27722168/role-of-histone-demethylases-in-cardiomyocytes-induced-to-hypertrophy
#3
Wendy Rosales, Juan Carulla, Jeison García, Diana Vargas, Fernando Lizcano
Epigenetic changes induced by histone demethylases play an important role in differentiation and pathological changes in cardiac cells. However, the role of the jumonji family of demethylases in the development of cardiac hypertrophy remains elusive. In this study, the presence of different histone demethylases in cardiac cells was evaluated after hypertrophy was induced with neurohormones. A cell line from rat cardiomyocytes was used as a biological model. The phenotypic profiles of the cells, as well as the expression of histone demethylases, were studied through immunofluorescence, transient transfection, western blot, and qRT-PCR analysis after inducing hypertrophy by angiotensin II and endothelin-1...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27626669/kdm4a-coactivates-e2f1-to-regulate-the-pdk-dependent-metabolic-switch-between-mitochondrial-oxidation-and-glycolysis
#4
Ling-Yu Wang, Chiu-Lien Hung, Yun-Ru Chen, Joy C Yang, Junjian Wang, Mel Campbell, Yoshihiro Izumiya, Hong-Wu Chen, Wen-Ching Wang, David K Ann, Hsing-Jien Kung
The histone lysine demethylase KDM4A/JMJD2A has been implicated in prostate carcinogenesis through its role in transcriptional regulation. Here, we describe KDM4A as a E2F1 coactivator and demonstrate a functional role for the E2F1-KDM4A complex in the control of tumor metabolism. KDM4A associates with E2F1 on target gene promoters and enhances E2F1 chromatin binding and transcriptional activity, thereby modulating the transcriptional profile essential for cancer cell proliferation and survival. The pyruvate dehydrogenase kinases (PDKs) PDK1 and PDK3 are direct targets of KDM4A and E2F1 and modulate the switch between glycolytic metabolism and mitochondrial oxidation...
September 13, 2016: Cell Reports
https://www.readbyqxmd.com/read/27612013/silencing-the-epigenetic-silencer-kdm4a-for-trail-and-dr5-simultaneous-induction-and-antitumor-therapy
#5
Junjian Wang, Haibin Wang, Ling-Yu Wang, Demin Cai, Zhijian Duan, Yanhong Zhang, Peng Chen, June X Zou, Jianzhen Xu, Xinbin Chen, Hsing-Jien Kung, Hong-Wu Chen
Recombinant TRAIL and agonistic antibodies to death receptors (DRs) have been in clinical trial but displayed limited anti-cancer efficacy. Lack of functional DR expression in tumors is a major limiting factor. We report here that chromatin regulator KDM4A/JMJD2A, not KDM4B, has a pivotal role in silencing tumor cell expression of both TRAIL and its receptor DR5. In TRAIL-sensitive and -resistant cancer cells of lung, breast and prostate, KDM4A small-molecule inhibitor compound-4 (C-4) or gene silencing strongly induces TRAIL and DR5 expression, and causes TRAIL-dependent apoptotic cell death...
November 1, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27266524/continual-removal-of-h3k9-promoter-methylation-by-jmjd2-demethylases-is-vital-for-esc-self-renewal-and-early-development
#6
Marianne Terndrup Pedersen, Susanne Marije Kooistra, Aliaksandra Radzisheuskaya, Anne Laugesen, Jens Vilstrup Johansen, Daniel Geoffrey Hayward, Jakob Nilsson, Karl Agger, Kristian Helin
Chromatin-associated proteins are essential for the specification and maintenance of cell identity. They exert these functions through modulating and maintaining transcriptional patterns. To elucidate the functions of the Jmjd2 family of H3K9/H3K36 histone demethylases, we generated conditional Jmjd2a/Kdm4a, Jmjd2b/Kdm4b and Jmjd2c/Kdm4c/Gasc1 single, double and triple knockout mouse embryonic stem cells (ESCs). We report that while individual Jmjd2 family members are dispensable for ESC maintenance and embryogenesis, combined deficiency for specifically Jmjd2a and Jmjd2c leads to early embryonic lethality and impaired ESC self-renewal, with spontaneous differentiation towards primitive endoderm under permissive culture conditions...
July 15, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27257215/jmjd2-kdm4-demethylases-are-required-for-expression-of-il3ra-and-survival-of-acute-myeloid-leukemia-cells
#7
Karl Agger, Satoru Miyagi, Marianne Terndrup Pedersen, Susanne M Kooistra, Jens Vilstrup Johansen, Kristian Helin
Acute myeloid leukemias (AMLs) with a rearrangement of the mixed-linage leukemia (MLL) gene are aggressive hematopoietic malignancies. Here, we explored the feasibility of using the H3K9- and H3K36-specific demethylases Jmjd2/Kdm4 as putative drug targets in MLL-AF9 translocated leukemia. Using Jmjd2a, Jmjd2b, and Jmjd2c conditional triple-knockout mice, we show that Jmjd2/Kdm4 activities are required for MLL-AF9 translocated AML in vivo and in vitro. We demonstrate that expression of the interleukin 3 receptor α (Il3ra also known as Cd123) subunit is dependent on Jmjd2/Kdm4 through a mechanism involving removal of H3K9me3 from the promoter of the Il3ra gene...
June 1, 2016: Genes & Development
https://www.readbyqxmd.com/read/27109047/ets-transcription-factor-erg-cooperates-with-histone-demethylase-kdm4a
#8
Tae-Dong Kim, Sook Shin, Ralf Janknecht
ERG (ETS-related gene) is a member of the ETS (erythroblast transformation-specific) family of transcription factors. Overexpression of the ERG transcription factor is observed in half of all prostate tumors and is an underlying cause of this disease. However, the mechanisms involved in the functions of ERG are still not fully understood. In the present study, we showed that ERG can directly bind to KDM4A (also known as JMJD2A), a histone demethylase that particularly demethylates lysine 9 on histone H3. ERG and KDM4A cooperated in upregulating the promoter of Yes-associated protein 1 (YAP1), a downstream effector in the Hippo signaling pathway and crucial growth regulator...
June 2016: Oncology Reports
https://www.readbyqxmd.com/read/27099369/epigenetic-activation-of-sox2-gene-in-the-developing-vertebrate-neural-plate
#9
Santiago O Bouzas, Melisa S Marini, Eliana Torres Zelada, Ailín L Buzzi, David A Morales Vicente, Pablo H Strobl-Mazzulla
One of the earliest manifestations of neural induction is onset of expression of the neural marker Sox2, mediated by the activation of the enhancers N1 and N2. By using loss and gain of function, we find that Sox2 expression requires the activity of JmjD2A and the Msk1 kinase, which can respectively demethylate the repressive H3K9me3 mark and phosphorylate the activating H3S10 (H3S10ph) mark. Bimolecular fluorescence complementation reveals that the adaptor protein 14-3-3, known to bind to H3S10ph, interacts with JMJD2A and may be involved in its recruitment to regulatory regions of the Sox2 gene...
June 15, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/26971619/substituted-2-2-aminopyrimidin-4-yl-pyridine-4-carboxylates-as-potent-inhibitors-of-jumonjic-domain-containing-histone-demethylases
#10
Martin Roatsch, Dina Robaa, Martin Pippel, Joanne E Nettleship, Yamini Reddivari, Louise E Bird, Inga Hoffmann, Henriette Franz, Raymond J Owens, Roland Schüle, Ralf Flaig, Wolfgang Sippl, Manfred Jung
BACKGROUND: Aberrant expression of iron(II)- and 2-oxoglutarate-dependent JumonjiC histone demethylases has been linked to cancer. Potent demethylase inhibitors are drug candidates and biochemical tools to elucidate the functional impact of demethylase inhibition. METHODS & RESULTS: Virtual screening identified a novel lead scaffold against JMJD2A with low-micromolar potency in vitro. Analogs were acquired from commercial sources respectively synthesized in feedback with biological testing...
September 2016: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/26907765/erratum-to-jmjd2a-dependent-silencing-of-sp1-in-advanced-breast-cancer-promotes-metastasis-by-downregulation-of-diras3
#11
Liliang Li, Pan Gao, Yuhua Li, Yiwen Shen, Jianhui Xie, Daming Sun, Aimin Xue, Ziqin Zhao, Zude Xu, Mingchang Zhang, Beixu Li, Jieqing Jiang
No abstract text is available yet for this article.
February 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/26663343/dioxygen-binding-in-the-active-site-of-histone-demethylase-jmjd2a-and-the-role-of-the-protein-environment
#12
Wilian A Cortopassi, Robert Simion, Charles E Honsby, Tanos C C França, Robert S Paton
Invited for the cover of this issue is the group of Robert S. Paton at the University of Oxford and his collaborators from Brazil and the Czech Republic. The image depicts histone-enzyme complexation and the chemical interactions inside the active site that define the mode of action. Read the full text of the article at 10.1002/chem.201502983.
December 21, 2015: Chemistry: a European Journal
https://www.readbyqxmd.com/read/26530537/iox1-a-jmjd2a-inhibitor-suppresses-the-proliferation-and-migration-of-vascular-smooth-muscle-cells-induced-by-angiotensin%C3%A2-ii-by-regulating-the-expression-of-cell-cycle-related-proteins
#13
Qi Hu, Jing Chen, Jing Zhang, Changwu Xu, Shuo Yang, Hong Jiang
The epigenetic modification of vascular smooth muscle cell (VSMC) phenotypic switching, proliferation, migration, apoptosis and extracellular matrix synthesis is known to occur in atherosclerosis. The aim of the present study was to investigate the effects of IOX1, a Jumonji domain-containing 2A (JMJD2A) inhibitor, on regulation of the cell cycle in angiotensin II (Ang II)-stimulated VSMCs and to elucidate the possible mechanisms involved. The proliferation and migration of the Ang II-stimulated VSMCs in the presence or absence of IOX1 were evaluated in vitro...
January 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/26491978/novel-5-carboxy-8-hq-based-histone-demethylase-jmjd2a-inhibitors-introduction-of-an-additional-carboxyl-group-at-the-c-2-position-of-quinoline
#14
Taotao Feng, Dongdong Li, Hai Wang, Jian Zhuang, Fang Liu, Qichao Bao, Yonghua Lei, Weilin Chen, Xiaojin Zhang, Xiaoli Xu, Haopeng Sun, Qidong You, Xiaoke Guo
A series of JMJD2A inhibitors had been designed by analyzing the binding mode of 5-carboxy-8-hydroxyquinoline (5-carboxy-8-HQ) with JMJD2A. The inhibitory activity of the synthesized compounds against JMJD2A was determined, followed by docking simulations to understand the structure-activity relationships. Compounds with potent JMJD2A inhibitory activity demonstrated outstanding selectivity for JMJD2A over PHD2. Several potent compounds were selected to evaluate their anti-proliferative activity on tumor cell lines...
November 13, 2015: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/26461474/mir137-is-an-androgen-regulated-repressor-of-an-extended-network-of-transcriptional-coregulators
#15
Emeli M Nilsson, Kristian B Laursen, Jonathan Whitchurch, Andrew McWilliam, Niels Ødum, Jenny L Persson, David M Heery, Lorraine J Gudas, Nigel P Mongan
Androgens and the androgen receptor (AR) play crucial roles in male development and the pathogenesis and progression of prostate cancer (PCa). The AR functions as a ligand dependent transcription factor which recruits multiple enzymatically distinct epigenetic coregulators to facilitate transcriptional regulation in response to androgens. Over-expression of AR coregulators is implicated in cancer. We have shown that over-expression of KDM1A, an AR coregulator, contributes to PCa recurrence by promoting VEGFA expression...
November 3, 2015: Oncotarget
https://www.readbyqxmd.com/read/26356263/histone-demethylase-jmjd2a-inhibition-attenuates-neointimal-hyperplasia-in-the-carotid-arteries-of-balloon-injured-diabetic-rats-via-transcriptional-silencing-inflammatory-gene-expression-in-vascular-smooth-muscle-cells
#16
Hu Qi, Zhang Jing, Wu Xiaolin, Xu Changwu, Hu Xiaorong, Yang Jian, Chen Jing, Jiang Hong
BACKGROUND/AIMS: Diabetic patients suffer from severe neointimal hyperplasia following angioplasty. The epigenetic abnormalities are increasingly considered to be relevant to the pathogenesis of diabetic cardiovascular complications. But the epigenetic mechanisms linking diabetes and coronary restenosis have not been fully elucidated. In this study, we explored the protective effect and underlying mechanisms of demethylases JMJD2A inhibition in balloon-injury induced neointimal formation in diabetic rats...
2015: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/26337137/tetrazolylhydrazides-as-selective-fragment-like-inhibitors-of-the-jumonjic-domain-containing-histone-demethylase-kdm4a
#17
Nicole Rüger, Martin Roatsch, Thomas Emmrich, Henriette Franz, Roland Schüle, Manfred Jung, Andreas Link
The JumonjiC-domain-containing histone demethylase 2A (JMJD2A, KDM4A) is a key player in the epigenetic regulation of gene expression. Previous publications have shown that both elevated and lowered enzyme levels are associated with certain types of cancer, and therefore the definite role of KDM4A in oncogenesis remains elusive. To identify a novel molecular starting point with favorable physicochemical properties for the investigation of the physiological role of KDM4A, we screened a number of molecules bearing an iron-chelating moiety by using two independent assays...
November 2015: ChemMedChem
https://www.readbyqxmd.com/read/26240495/epigenetic-role-of-histone-3-lysine-methyltransferase-and-demethylase-in-regulating-apoptosis-predicting-the-recurrence-of-atypical-meningioma
#18
Sang Hyuk Lee, Eun Hee Lee, Sung-Hun Lee, Young Min Lee, Hyung Dong Kim, Young Zoon Kim
Alteration of apoptosis is related with progression and recurrence of atypical meningiomas (AMs). However, no comprehensive study has been conducted regarding histone modification regulating apoptosis in AMs. This study aimed to determine the prognostic values of certain apoptosis-associated factors, and examine the role of histone modification on apoptosis in AMs. The medical records of 67 patients with AMs, as diagnosed during recent 13 yr, were reviewed retrospectively. Immunohistochemical staining was performed on archived paraffin-embedded tissues for pro-apoptotic factors (CASP3, IGFBP, TRAIL-R1, BAX, and XAF1), anti-apoptotic factors (survivin, ERK, RAF1, MDM2, and BCL2), and the histone modifying enzymes (MLL2, RIZ, EZH1, NSD2, KDM5c, JMJD2a, UTX, and JMJD5)...
August 2015: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/25883088/novel-scaffolds-of-cell-active-histone-demethylase-inhibitors-identified-from-high-throughput-screening
#19
Wei Wang, Laura J Marholz, Xiang Wang
Jumonji C domain-containing histone demethylases (JHDMs) are epigenetic proteins capable of demethylating methylated lysine residues on histones proteins and for which high-quality chemical probes and eventual therapeutic leads are highly desirable. To expand the extent of known scaffolds targeting JHDMs, we initiated an unbiased high-throughput screening approach using a fluorescence polarization (FP)-based competitive binding assay we recently reported for JHDM1A (aka KDM2A). In total, 14,400 compounds in the HitFinder collection v...
July 2015: Journal of Biomolecular Screening
https://www.readbyqxmd.com/read/25843056/selective-inhibition-of-prostaglandin-e2-receptors-ep2-and-ep4-modulates-dna-methylation-and-histone-modification-machinery-proteins-in-human-endometriotic-cells
#20
Joe A Arosh, JeHoon Lee, Anna Starzinski-Powitz, Sakhila K Banu
Endometriosis is an inflammatory gynecological disease of reproductive-age women. The prevalence of endometriosis is 5-10% in reproductive-age women. Modern medical treatments are directed to inhibit the action of estrogen in endometriotic cells. However, hormonal therapies targeting estrogen can be prescribed only for a short time because of their undesirable side effects. Recent studies from our laboratory, using human endometriotic epithelial cell line 12Z and stromal cell line 22B derived from red lesion, discovered that selective inhibition of prostaglandin E2 (PGE2) receptors EP2 and EP4 inhibits adhesion, invasion, growth, and survival of 12Z and 22B cells by modulating integrins, MMPs and TIMPs, cell cycle, survival, and intrinsic apoptotic pathways, suggesting multiple epigenetic mechanisms...
July 5, 2015: Molecular and Cellular Endocrinology
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