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Histone demethylation

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https://www.readbyqxmd.com/read/29162512/mmp9-gene-expression-regulation-by-intragenic-epigenetic-modifications-in-breast-cancer
#1
Liliane M B Klassen, Andressa Chequin, Graciele C M Manica, Isis V Biembengut, Mariana B Toledo, Valter A Baura, Fábio de O Pedrosa, Edneia A S Ramos, Fabrício F Costa, Emanuel M De Souza, Giseli Klassen
Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among women worldwide. Metastasis remains a major challenge for the clinical management and prognosis of patients with cancer. The metalloprotease MMP-9 plays a critical role in the first step of metastasis through extracellular matrix degradation. In this study, our goal was to determine the effect of epigenetic mechanisms in the promoter and intragenic region of this gene and to correlate it to the levels of expression of MMP9 in breast cancer cell lines...
November 18, 2017: Gene
https://www.readbyqxmd.com/read/29160132/active-h3k27me3-demethylation-by-kdm6b-is-required-for-normal-development-of-bovine-preimplantation-embryos
#2
Nhi Chung, Yanina S Bogliotti, Wei Ding, Marcela Vilarino, Kazuki Takahashi, James L Chitwood, Richard M Schultz, Pablo J Ross
The substantial epigenetic remodeling that occurs during early stages of mammalian embryonic development likely contributes to reprogramming the parental genomes from a differentiated to a totipotent state and activation of the embryonic genome. Trimethylation of lysine 27 of histone 3 (H3K27me3) is a repressive mark that undergoes global dynamic changes during preimplantation development of several species. To ascertain the role of H3K27me3 in bovine preimplantation development we perturbed the activity of KDM6B, which demethylates H3K27me3...
November 21, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29133832/jmjd8-is-a-novel-endoplasmic-reticulum-protein-with-a-jmjc-domain
#3
Kok Siong Yeo, Ming Cheang Tan, Yat-Yuen Lim, Chee-Kwee Ea
Jumonji C (JmjC) domain-containing proteins have been shown to regulate cellular processes by hydroxylating or demethylating histone and non-histone targets. JMJD8 belongs to the JmjC domain-only family that was recently shown to be involved in angiogenesis and TNF-induced NF-κB signaling. Here, we employed bioinformatic analysis and immunofluorescence microscopy to examine the physiological properties of JMJD8. We demonstrated that JMJD8 localizes to the lumen of endoplasmic reticulum and that JMJD8 forms dimers or oligomers in vivo...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29102482/vitamin-c-a-new-player-in-regulation-of-the-cancer-epigenome
#4
REVIEW
Linn Gillberg, Andreas D Ørskov, Minmin Liu, Laurine B S Harsløf, Peter A Jones, Kirsten Grønbæk
Over the past few years it has become clear that vitamin C, as a provider of reduced iron, is an essential factor for the function of epigenetic regulators that initiate the demethylation of DNA and histones. Vitamin C deficiency is rare in the general population, but is frequently observed in patients with cancer. Genes encoding epigenetic regulators are often mutated in cancer, underscoring their central roles in carcinogenesis. In hematological cancers, such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), drugs that reverse epigenetic aberrations are now the standard of care...
November 1, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29100410/chidamide-and-decitabine-can-synergistically-induce-apoptosis-of-hodgkin-lymphoma-cells-by-up-regulating-the-expression-of-pu-1-and-klf4
#5
Tao Jiang, Fujue Wang, Lianjie Hu, Xiaomin Cheng, Yuhuan Zheng, Ting Liu, Yongqian Jia
Epigenetic abnormalities play important roles in the pathogenesis of Hodgkin lymphoma (HL). Highly expressed class I histone acetyltransferase (HDAC) and hyper-methylation of the promoter region of tumor suppressor genes have been demonstrated in Hodgkin lymphoma. In this paper, we investigated the synergistic effects of combination treatment of chidamide, a selective HDAC inhibitor, and decitabine, a demethylation agent, for HL cell lines and explored a new strategy for treating HL. The apoptosis rates, cell cycle, mitochondrial transmembrane potentials, epigenetic changes and gene expression of HL cell lines treated with chidamide as a single agent and in combination with decitabine were tested...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29100015/an-endosirna-based-repression-mechanism-counteracts-transposon-activation-during-global-dna-demethylation-in-embryonic-stem-cells
#6
Rebecca V Berrens, Simon Andrews, Dominik Spensberger, Fátima Santos, Wendy Dean, Poppy Gould, Jafar Sharif, Nelly Olova, Tamir Chandra, Haruhiko Koseki, Ferdinand von Meyenn, Wolf Reik
Erasure of DNA methylation and repressive chromatin marks in the mammalian germline leads to risk of transcriptional activation of transposable elements (TEs). Here, we used mouse embryonic stem cells (ESCs) to identify an endosiRNA-based mechanism involved in suppression of TE transcription. In ESCs with DNA demethylation induced by acute deletion of Dnmt1, we saw an increase in sense transcription at TEs, resulting in an abundance of sense/antisense transcripts leading to high levels of ARGONAUTE2 (AGO2)-bound small RNAs...
November 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29099280/variant-histone-h2afv-reprograms-dna-methylation-during-early-zebrafish-development
#7
Bhavani Madakashira, Laura Corbett, Chi Zhang, Pier Paoli, John W Casement, Jelena Mann, Kirsten C Sadler, Derek A Mann
The DNA methylome is re-patterned during discrete phases of vertebrate development. In zebrafish, there are two waves of global DNA demethylation and re-methylation: the first occurs prior to gastrulation when the parental methylome is changed to the zygotic pattern and the second occurs after formation of the embryonic body axis, during organ specification. The occupancy of the histone variant H2A.Z and regions of DNA methylation are generally anti-correlated, and it has been proposed that H2A.Z restricts the boundaries of highly methylated regions...
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
#8
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, mRNA, 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 31, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29074395/epigenetics-of-malignant-melanoma
#9
REVIEW
Bruce Moran, Romina Silva, Antoinette S Perry, William M Gallagher
Patients with malignant melanoma generally have a good prognosis if the disease presents prior to metastasis. Due to progress with targeted and immunotherapies, the median survival of metastatic melanoma patients is now over 2 years. The disease is characterised by one of the highest somatic mutation rates observed amongst cancer types, with a specific mutational signature based on UV radiation damage evident. Highly prevalent mutations, such as the BRAF(V600E), in the MAPK cascade indicate truncal involvement of this pathway in the earliest stage of melanoma...
October 23, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29073101/utx-guided-neural-crest-function-underlies-craniofacial-features-of-kabuki-syndrome
#10
Karl B Shpargel, Joshua Starmer, Chaochen Wang, Kai Ge, Terry Magnuson
Kabuki syndrome, a congenital craniofacial disorder, manifests from mutations in an X-linked histone H3 lysine 27 demethylase (UTX/KDM6A) or a H3 lysine 4 methylase (KMT2D). However, the cellular and molecular etiology of histone-modifying enzymes in craniofacial disorders is unknown. We now establish Kabuki syndrome as a neurocristopathy, whereby the majority of clinical features are modeled in mice carrying neural crest (NC) deletion of UTX, including craniofacial dysmorphism, cardiac defects, and postnatal growth retardation...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29069809/human-papillomavirus-dysregulates-the-cellular-apparatus-controlling-the-methylation-status-of-h3k27-in-different-human-cancers-to-consistently-alter-gene-expression-regardless-of-tissue-of-origin
#11
Steven F Gameiro, Bart Kolendowski, Ali Zhang, John W Barrett, Anthony C Nichols, Joe Torchia, Joe S Mymryk
High-risk human papillomaviruses (HPV) cause cancer at multiple distinct anatomical locations. Regardless of the tissue of origin, most HPV positive (HPV+) cancers show highly upregulated expression of the p16 product of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene. Paradoxically, HPV+ tumor cells require continuous expression of this tumor suppressor for survival. Thus, restoration of normal p16 regulation has potential therapeutic value against HPV induced cancers. Normally, p16 transcription is tightly controlled at the epigenetic level via polycomb repressive complex-mediated tri-methylation of histone 3 lysine 27 (H3K27me3)...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29059406/dynamic-site-specific-recruitment-of-rbp2-by-pocket-protein-p130-modulates-h3k4-methylation-on-e2f-responsive-promoters
#12
Zaffer Ullah Zargar, Mallikharjuna Rao Kimidi, Shweta Tyagi
The Histone 3 lysine 4 methylation (H3K4me3) mark closely correlates with active transcription. E2F-responsive promoters display dynamic changes in H3K4 methylation during the course of cell cycle progression. However, how and when these marks are reset, is not known. Here we show that the retinoblastoma binding protein RBP2/KDM5A, capable of removing tri-methylation marks on H3K4, associates with the E2F4 transcription factor via the pocket protein-p130-in a cell-cycle-stage specific manner. The association of RBP2 with p130 is LxCxE motif dependent...
October 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29054488/the-histone-demethylase-jmjd2a-regulates-the-expression-of-bdnf-and-mediates-neuropathic-pain-in-mice
#13
Junfei Zhou, Fang Wang, Chang Xu, Zipeng Zhou, Wei Zhang
JMJD2A is a JmjC histone demethylase that catalyzes the demethylation of di- and trimethylated Lys9 and Lys36 in histone H3 (H3K9me2/3 and H3K36me2/3). The role of spinal JMJD2A-dependent histone demethylation in nociception hypersensitivity development remains elusive. Here we reported that the JMJD2A responded to neuropathic pain and participated in the maintenance of neuropathic pain. The mRNA and protein levels of Jmjd2a were significantly increased in the neurons of mouse undergoing neuropathic pain induced by sciatic nerve chronic constrictive injury (CCI) or unilateral spared nerve injury (SNI)...
October 18, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29053963/hydrilla-verticillata-employs-two-different-ways-to-affect-dna-methylation-under-excess-copper-stress
#14
Danlu Shi, Kai Zhuang, Yan Xia, Changhua Zhu, Chen Chen, Zhubing Hu, Zhenguo Shen
Because of the accumulation of heavy metals, Hydrilla verticillata (L.f.) Royle, a rooted submerged perennial aquatic herb, is being developed as a potential tool to clean the aquatic ecosystem polluted by heavy metals. However, its physiological responses for heavy metal remain to be elucidated. Here, through employing proteomics approach, we found that excess Cu significantly induced the expressions of four DNA methylation related proteins in H. verticillata, which were the homologues of two domains rearranged methyltransferases (DRM), a methyltransferases chromomethylase (CMT) and a histone H3 lysine-9 specific SUVH6-like (SUVH6)...
October 14, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/29042477/kdm3a-mediated-demethylation-of-histone-h3-lysine-9-facilitates-the-chromatin-binding-of-neurog2-during-neurogenesis
#15
Hao Lin, Xuechen Zhu, Geng Chen, Lei Song, Li Gao, Aftab A Khand, Ying Chen, Gufa Lin, Qinghua Tao
Neurog2 is a crucial regulator of neuronal fate specification and differentiation in vivo and in vitro However, it remains unclear how Neurog2 transactivates neuronal genes that are silenced by repressive chromatin. Here, we provide evidence that the histone H3 lysine 9 demethylase KDM3A facilitates the Xenopus Neurog2 (formerly known as Xngnr1) chromatin accessibility during neuronal transcription. Loss-of-function analyses reveal that KDM3A is not required for the transition of naive ectoderm to neural progenitor cells but is essential for primary neuron formation...
October 15, 2017: Development
https://www.readbyqxmd.com/read/29030483/rbpj-cbf1-interacts-with-l3mbtl3-mbt1-to-promote-repression-of-notch-signaling-via-histone-demethylase-kdm1a-lsd1
#16
Tao Xu, Sung-Soo Park, Benedetto Daniele Giaimo, Daniel Hall, Francesca Ferrante, Diana M Ho, Kazuya Hori, Lucas Anhezini, Iris Ertl, Marek Bartkuhn, Honglai Zhang, Eléna Milon, Kimberly Ha, Kevin P Conlon, Rork Kuick, Brandon Govindarajoo, Yang Zhang, Yuqing Sun, Yali Dou, Venkatesha Basrur, Kojo Sj Elenitoba-Johnson, Alexey I Nesvizhskii, Julian Ceron, Cheng-Yu Lee, Tilman Borggrefe, Rhett A Kovall, Jean-François Rual
Notch signaling is an evolutionarily conserved signal transduction pathway that is essential for metazoan development. Upon ligand binding, the Notch intracellular domain (NOTCH ICD) translocates into the nucleus and forms a complex with the transcription factor RBPJ (also known as CBF1 or CSL) to activate expression of Notch target genes. In the absence of a Notch signal, RBPJ acts as a transcriptional repressor. Using a proteomic approach, we identified L3MBTL3 (also known as MBT1) as a novel RBPJ interactor...
November 2, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29018328/intermittent-ethanol-during-adolescence-leads-to-lasting-behavioral-changes-in-adulthood-and-alters-gene-expression-and-histone-methylation-in-the-pfc
#17
Jennifer T Wolstenholme, Tariq Mahmood, Guy M Harris, Shahroze Abbas, Michael F Miles
Adolescents primarily consume alcohol in binges, which can be particularly harmful to the developing frontal cortex and increase risk for an adult alcohol use disorder. We conducted a study investigating immediate and long lasting changes to the prefrontal cortex (PFC) transcriptome to determine the molecular mechanisms underlying adult ethanol behavioral sensitivity following binge ethanol in adolescence. DBA/2J mice were orally dosed with 4 g/kg ethanol intermittently from day 29 to 42. Adolescent mice were tested for anxiety-like behavior and ethanol sensitivity using the loss of righting reflex task...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28991226/lsd1-promotes-s-phase-entry-and-tumorigenesis-via-chromatin-co-occupation-with-e2f1-and-selective-h3k9-demethylation
#18
Y He, Y Zhao, L Wang, L R Bohrer, Y Pan, L Wang, H Huang
Histone H3 lysine-9 (H3K9) methylation is essential for retinoblastoma protein (RB)-mediated heterochromatin formation, epigenetic silencing of S-phase genes and permanent cell cycle arrest or cellular senescence. Besides as an H3K4 demethylase, lysine-specific demethylase-1 (LSD1) has been shown to promote H3K9 demethylation. However, it is unexplored whether LSD1 has a causal role in regulating cell cycle entry and senescence. Here we demonstrate that genetic depletion or pharmacological inhibition of LSD1 triggers G1 arrest and cellular senescence...
October 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28972166/histone-arginine-demethylase-jmjd6-is-linked-to-stress-granule-assembly-through-demethylation-of-the-stress-granule-nucleating-protein-g3bp1
#19
Wei-Chih Tsai, Lucas C Reineke, Antrix Jain, Sung Yun Jung, Richard E Lloyd
Stress granules (SG) are membrane-less organelles that are condensates of stalled translation initiation complexes and mRNAs. SG formation is a cytoprotective response to environmental stress and results from protein interactions involving regions of low amino acid complexity and poorly defined post-translational modifications of SG components. Many RNA binding proteins are methylated and we previously demonstrated that the potent SG nucleating protein G3BP1 is methylated by protein arginine methyltransferase 1 and 5 (PRMT1 and PRMT5)...
September 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28949961/rescuing-the-aberrant-sex-development-of-h3k9-demethylase-jmjd1a-deficient-mice-by-modulating-h3k9-methylation-balance
#20
Shunsuke Kuroki, Naoki Okashita, Shoko Baba, Ryo Maeda, Shingo Miyawaki, Masashi Yano, Miyoko Yamaguchi, Satsuki Kitano, Hitoshi Miyachi, Akihiro Itoh, Minoru Yoshida, Makoto Tachibana
Histone H3 lysine 9 (H3K9) methylation is a hallmark of heterochromatin. H3K9 demethylation is crucial in mouse sex determination; The H3K9 demethylase Jmjd1a deficiency leads to increased H3K9 methylation at the Sry locus in embryonic gonads, thereby compromising Sry expression and causing male-to-female sex reversal. We hypothesized that the H3K9 methylation level at the Sry locus is finely tuned by the balance in activities between the H3K9 demethylase Jmjd1a and an unidentified H3K9 methyltransferase to ensure correct Sry expression...
September 2017: PLoS Genetics
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