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Histone demethylation

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https://www.readbyqxmd.com/read/29782530/histone-methylation-changes-are-required-for-life-cycle-progression-in-the-human-parasite-schistosoma-mansoni
#1
David Roquis, Aaron Taudt, Kathrin K Geyer, Gilda Padalino, Karl F Hoffmann, Nancy Holroyd, Matt Berriman, Benoît Aliaga, Cristian Chaparro, Christoph Grunau, Ronaldo de Carvalho Augusto
Epigenetic mechanisms and chromatin structure play an important role in development. Their impact is therefore expected to be strong in parasites with complex life cycles and multiple, strikingly different, developmental stages, i.e. developmental plasticity. Some studies have already described how the chromatin structure, through histone modifications, varies from a developmental stage to another in a few unicellular parasites. However, this, to our knowledge, has never been done before in multicellular metazoan parasites...
May 21, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29780815/endometriosis-malignant-transformation-epigenetics-as-a-probable-mechanism-in-ovarian-tumorigenesis
#2
REVIEW
Jiaxing He, Weiqin Chang, Chunyang Feng, Manhua Cui, Tianmin Xu
Endometriosis, defined as the presence of ectopic endometrial glands and stroma outside the uterine cavity, is a chronic, hormone-dependent gynecologic disease affecting millions of women across the world, with symptoms including chronic pelvic pain, dysmenorrhea, dyspareunia, dysuria, and subfertility. In addition, there is well-established evidence that, although endometriosis is considered benign, it is associated with an increased risk of malignant transformation, with the involvement of various mechanisms of development...
2018: International Journal of Genomics
https://www.readbyqxmd.com/read/29774113/ezh2-inhibitors-sensitize-myeloma-cell-lines-to-panobinostat-resulting-in-unique-combinatorial-transcriptomic-changes
#3
Taylor Harding, Jessica Swanson, Brian Van Ness
Multiple myeloma (MM) remains a largely incurable hematologic cancer due to an inability to broadly target inevitable drug-resistant relapse. Epigenetic abnormalities are abundantly present in multiple myeloma and have increasingly demonstrated critical roles for tumor development and relapse to standard therapies. Accumulating evidence suggests that the histone methyltransferase EZH2 is aberrantly active in MM. We tested the efficacy of EZH2 specific inhibitors in a large panel of human MM cell lines (HMCLs) and found that only a subset of HMCLs demonstrate single agent sensitivity despite ubiquitous global H3K27 demethylation...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29769286/targeted-inhibition-of-histone-h3k27-demethylation-is-effective-in-high-risk-neuroblastoma
#4
Timothy L Lochmann, Krista M Powell, Jungoh Ham, Konstantinos V Floros, Daniel A R Heisey, Richard I J Kurupi, Marissa L Calbert, Maninderjit S Ghotra, Patricia Greninger, Mikhail Dozmorov, Madhu Gowda, Andrew J Souers, C Patrick Reynolds, Cyril H Benes, Anthony C Faber
High-risk neuroblastoma is often distinguished by amplification of MYCN and loss of differentiation potential. We performed high-throughput drug screening of epigenetic-targeted therapies across a large and diverse tumor cell line panel and uncovered the hypersensitivity of neuroblastoma cells to GSK-J4, a small-molecule dual inhibitor of lysine 27 of histone 3 (H3K27) demethylases ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX), and histone demethylase Jumonji D3 (JMJD3). Mechanistically, GSK-J4 induced neuroblastoma differentiation and endoplasmic reticulum (ER) stress, with accompanying up-regulation of p53 up-regulated modulator of apoptosis (PUMA) and induction of cell death...
May 16, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29763382/kdm2b-is-a-histone-h3k79-demethylase-and-induces-transcriptional-repression-via-sirtuin-1-mediated-chromatin-silencing
#5
Joo-Young Kang, Ji-Young Kim, Kee-Beom Kim, Jin Woo Park, Hana Cho, Ja Young Hahm, Yun-Cheol Chae, Daehwan Kim, Hyun Kook, Sangmyeong Rhee, Nam-Chul Ha, Sang-Beom Seo
The methylation of histone H3 lysine 79 (H3K79) is an active chromatin marker and is prominent in actively transcribed regions of the genome; however, demethylase of H3K79 remains unknown despite intensive research. Here, we show that KDM2B, also known as FBXL10 and a member of the Jumonji C family of proteins known for its histone H3K36 demethylase activity, is a di- and trimethyl H3K79 demethylase. We demonstrate that KDM2B induces transcriptional repression of HOXA7 and MEIS1 via occupancy of promoters and demethylation of H3K79...
May 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29753027/jmjd3-inhibition-protects-against-isoproterenol-induced-cardiac-hypertrophy-by-suppressing-%C3%AE-mhc-expression
#6
Zhen Guo, Jing Lu, Jingyan Li, Panxia Wang, Zhenzhen Li, Yao Zhong, Kaiteng Guo, Junjian Wang, Jiantao Ye, Peiqing Liu
Jumonji domain-containing protein D3 (JMJD3), a histone 3 lysine 27 (H3K27) demethylase, has been extensively studied for their participation in development, cellular physiology and a variety of diseases. However, its potential roles in cardiovascular system remain unknown. In this study, we found that JMJD3 played a pivotal role in the process of cardiac hypertrophy. JMJD3 expression was elevated by isoproterenol (ISO) stimuli both in vitro and in vivo. Overexpression of wild-type JMJD3, but not the demethylase-defective mutant, promoted cardiomyocyte hypertrophy, as implied by increased cardiomyocyte surface area and the expression of hypertrophy marker genes...
May 9, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29747586/selective-modulation-of-local-linkages-between-active-transcription-and-oxidative-demethylation-activity-shapes-cardiomyocyte-specific-gene-body-epigenetic-status-in-mice
#7
Mayumi Oda, Shunichi Wakabayashi, N Ari Wijetunga, Shinsuke Yuasa, Hirokazu Enomoto, Ruri Kaneda, Sung Han Yoon, Nishant Mittal, Qiang Jing, Masako Suzuki, John M Greally, Keiichi Fukuda, Shinji Makino
BACKGROUND: Cell-type-specific genes exhibit heterogeneity in genomic contexts and may be subject to different epigenetic regulations through different gene transcriptional processes depending on the cell type involved. The gene-body regions (GBRs) of some cardiomyocyte (CM)-specific genes are long and highly hypomethylated in CMs. To explore the cell-type specificities of epigenetic patterns and functions, multiple epigenetic modifications of GBRs were compared among CMs, liver cells and embryonic stem cells (ESCs)...
May 10, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29741645/lsd1-coordinates-with-the-sin3a-hdac-complex-and-maintains-sensitivity-to-chemotherapy-in-breast-cancer
#8
Yang Yang, Wei Huang, Rongfang Qiu, Ruiqiong Liu, Yi Zeng, Jie Gao, Yu Zheng, Yongqiang Hou, Shuang Wang, Wenqian Yu, Shuai Leng, Dandan Feng, Yan Wang
Lysine-specific demethylase 1 (LSD1) was the first histone demethylase identified as catalysing the removal of mono- and di-methylation marks on histone H3-K4. Despite the potential broad action of LSD1 in transcription regulation, recent studies indicate that LSD1 may coordinate with multiple epigenetic regulatory complexes including CoREST/HDAC complex, NuRD complex, SIRT1, and PRC2, implying complicated mechanistic actions of this seemingly simple enzyme. Here, we report that LSD1 is also an integral component of the SIN3A/HDAC complex...
May 7, 2018: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/29712855/fact-complex-is-required-for-dna-demethylation-at-heterochromatin-during-reproduction-in-arabidopsis
#9
Jennifer M Frost, M Yvonne Kim, Guen Tae Park, Ping-Hung Hsieh, Miyuki Nakamura, Samuel J H Lin, Hyunjin Yoo, Jaemyung Choi, Yoko Ikeda, Tetsu Kinoshita, Yeonhee Choi, Daniel Zilberman, Robert L Fischer
The DEMETER (DME) DNA glycosylase catalyzes genome-wide DNA demethylation and is required for endosperm genomic imprinting and embryo viability. Targets of DME-mediated DNA demethylation reside in small, euchromatic, AT-rich transposons and at the boundaries of large transposons, but how DME interacts with these diverse chromatin states is unknown. The STRUCTURE SPECIFIC RECOGNITION PROTEIN 1 (SSRP1) subunit of the chromatin remodeler FACT (facilitates chromatin transactions), was previously shown to be involved in the DME-dependent regulation of genomic imprinting in Arabidopsis endosperm...
April 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29704505/research-on-epigenetic-mechanism-of-sfrp2-in-advanced-chronic-myeloid-leukemia
#10
Ziye Li, Jianmin Luo
Secreted frizzled-related protein 2 (SFRP2) has been reported to act as a tumor suppressors. This study aims to detect the biological role of SFRP2 in advanced chronic myeloid leukemia (CML). In this study we examined bone marrow samples from 45 CML patients and 10 healthy donors. K562 and KCL22 cells were cultured and treated with demethylation drug and histone deacetylase inhibitor (HDACi). KCL22 and K562 cells were transfected with lentiviral vector (LV)-SFRP2, LV-control. The cells were then subjected to proliferation and apoptosis assays, real time polymerase chain reaction (PCR), Methylation-specific PCR (MSP), Western blotting, co-immunoprecipitation (CoIP) and Chromatin immunoprecipitation (ChIP), We found that SFRP2 was down-regulated in the accelerated and blast phase of CML, whereas, the levels of WNT1, WNT3 and WNT5A were up-regulated in the accelerated and blast phase of CML...
April 25, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29691401/methylated-dnmt1-and-e2f1-are-targeted-for-proteolysis-by-l3mbtl3-and-crl4-dcaf5-ubiquitin-ligase
#11
Feng Leng, Jiekai Yu, Chunxiao Zhang, Salvador Alejo, Nam Hoang, Hong Sun, Fei Lu, Hui Zhang
Many non-histone proteins are lysine methylated and a novel function of this modification is to trigger the proteolysis of methylated proteins. Here, we report that the methylated lysine 142 of DNMT1, a major DNA methyltransferase that preserves epigenetic inheritance of DNA methylation patterns during DNA replication, is demethylated by LSD1. A novel methyl-binding protein, L3MBTL3, binds the K142-methylated DNMT1 and recruits a novel CRL4DCAF5 ubiquitin ligase to degrade DNMT1. Both LSD1 and PHF20L1 act primarily in S phase to prevent DNMT1 degradation by L3MBTL3-CRL4DCAF5 ...
April 24, 2018: Nature Communications
https://www.readbyqxmd.com/read/29686419/dynamics-of-the-epigenetic-landscape-during-the-maternal-to-zygotic-transition
#12
REVIEW
Melanie A Eckersley-Maslin, Celia Alda-Catalinas, Wolf Reik
A remarkable epigenetic remodelling process occurs shortly after fertilization, which restores totipotency to the zygote. This involves global DNA demethylation, chromatin remodelling, genome spatial reorganization and substantial transcriptional changes. Key to these changes is the transition from the maternal environment of the oocyte to an embryonic-driven developmental expression programme, a process termed the maternal-to-zygotic transition (MZT). Zygotic genome activation occurs predominantly at the two-cell stage in mice and the eight-cell stage in humans, yet the dynamics of its control are still mostly obscure...
April 23, 2018: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/29685975/inhibitors-of-both-the-n-methyl-lysyl-and-arginyl-demethylase-activities-of-the-jmjc-oxygenases
#13
Joanna Bonnici, Anthony Tumber, Akane Kawamura, Christopher J Schofield
The Jumonji C (JmjC) family of 2-oxoglutarate (2OG)-dependent oxygenases have established roles in the regulation of transcription via the catalysis of demethylation of N ε - methylated lysine residues in histone tails, especially the N - terminal tail of histone H3. Most human JmjC N ɛ -methyl lysine demethylases (KDMs) are complex enzymes, with 'reader domains' in addition to their catalytic domains. Recent biochemical evidence has shown that some, but not all, JmjC KDMs also have N ω - methyl arginyl demethylase (RDM) activity...
June 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29682202/ctcf-kdm4a-complex-correlates-with-histone-modifications-that-negatively-regulate-chd5-gene-expression-in-cancer-cell-lines
#14
Lissania Guerra-Calderas, Rodrigo González-Barrios, Carlos César Patiño, Nicolás Alcaraz, Marisol Salgado-Albarrán, David Cantú de León, Clementina Castro Hernández, Yesennia Sánchez-Pérez, Héctor Aquiles Maldonado-Martínez, Inti A De la Rosa-Velazquez, Fernanda Vargas-Romero, Luis A Herrera, Alejandro García-Carrancá, Ernesto Soto-Reyes
Histone demethylase KDM4A is involved in H3K9me3 and H3K36me3 demethylation, which are epigenetic modifications associated with gene silencing and RNA Polymerase II elongation, respectively. KDM4A is abnormally expressed in cancer, affecting the expression of multiple targets, such as the CHD5 gene. This enzyme localizes at the first intron of CHD5 , and the dissociation of KDM4A increases gene expression. In vitro assays showed that KDM4A-mediated demethylation is enhanced in the presence of CTCF, suggesting that CTCF could increase its enzymatic activity in vivo, however the specific mechanism by which CTCF and KDM4A might be involved in the CHD5 gene repression is poorly understood...
March 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29682190/the-jmjn-domain-as-a-dimerization-interface-and-a-targeted-inhibitor-of-kdm4-demethylase-activity
#15
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/29676649/asbestos-induces-epigenetic-repression-of-ras-association-domain-containing-protein-1-p16-kinase-4a-inhibitor-and-p14-alternative-reading-frame-in-normal-human-mesothelial-cells
#16
Sichuan Xi, Eden C Payabyab, David M Straughan, Emily S Reardon, Mary Zhang, Julie A Hong, R Taylor Ripley, Chuong D Hoang, David S Schrump
RATIONALE: Whereas asbestos burden has been linked to cytogenetic alterations in malignant pleural mesotheliomas, epigenetic aberrations induced by these fibers have not been fully delineated. OBJECTIVES: The objective of this study was to establish an in vitro model to characterize early epigenetic events potentially contributing to malignant pleural mesothelioma. METHODS: Normal human mesothelial cells (LP9 and LP3) were cultured with or without crocidolite asbestos fibers (1 or 2 μg/cm2 ) for up to 10 days...
April 2018: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/29674659/histone-demethylase-jmjd1a-coordinates-acute-and-chronic-adaptation-to-cold-stress-via-thermogenic-phospho-switch
#17
Yohei Abe, Yosuke Fujiwara, Hiroki Takahashi, Yoshihiro Matsumura, Tomonobu Sawada, Shuying Jiang, Ryo Nakaki, Aoi Uchida, Noriko Nagao, Makoto Naito, Shingo Kajimura, Hiroshi Kimura, Timothy F Osborne, Hiroyuki Aburatani, Tatsuhiko Kodama, Takeshi Inagaki, Juro Sakai
In acute cold stress in mammals, JMJD1A, a histone H3 lysine 9 (H3K9) demethylase, upregulates thermogenic gene expressions through β-adrenergic signaling in brown adipose tissue (BAT). Aside BAT-driven thermogenesis, mammals have another mechanism to cope with long-term cold stress by inducing the browning of the subcutaneous white adipose tissue (scWAT). Here, we show that this occurs through a two-step process that requires both β-adrenergic-dependent phosphorylation of S265 and demethylation of H3K9me2 by JMJD1A...
April 19, 2018: Nature Communications
https://www.readbyqxmd.com/read/29665845/deletion-of-hp1%C3%AE-in-cardiac-myocytes-affects-h4k20me3-levels-but-does-not-impact-cardiac-growth
#18
Kyohei Oyama, Danny El-Nachef, Chen Fang, Hidemi Kajimoto, Jeremy P Brown, Prim B Singh, W Robb MacLellan
BACKGROUND: Heterochromatin, which is formed when tri-methyl lysine 9 of histone H3 (H3K9me3) is bound by heterochromatin 1 proteins (HP1s), plays an important role in differentiation and senescence by silencing cell cycle genes. Cardiac myocytes (CMs) accumulate heterochromatin during differentiation and demethylation of H3K9me3 inhibits cell cycle gene silencing and cell cycle exit in CMs; however, it is unclear if this process is mediated by HP1s. In this study, we created a conditional CM-specific HP1 gamma (HP1γ) knockout (KO) mouse model and tested whether HP1γ is required for cell cycle gene silencing and cardiac growth...
April 17, 2018: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29663555/dehydroleucodine-inhibits-mitotic-clonal-expansion-during-adipogenesis-through-cell-cycle-arrest
#19
S Abood, M L Veisaga, L A López, M A Barbieri
Aberrant levels of preadipocyte differentiation, triggered by adipocyte hyperplasia and hypertrophy, results in the obesogenic phenotype. Obesity is a risk factor for several metabolic disorders. In this paper, dehydroleucodine inhibited the accumulation of lipid droplets and decreased the elevations of triglycerides, and this inhibitory effect occurred during the early stage of adipogenesis. Thus, not only did dehydroleucodine downregulate the expression of C/EBPα and PPARγ, it also strongly blocked the expression of C/EBPβ, an early stage biomarker of early adipogenesis, in a concentration-dependent manner...
April 16, 2018: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/29656462/kdm1a-regulated-the-osteo-dentinogenic-differentiation-process-of-the-stem-cells-of-the-apical-papilla-via-binding-with-plod2
#20
Lijun Wang, Haoqing Yang, Xiao Lin, Yangyang Cao, Peipei Gao, Ying Zheng, Zhipeng Fan
OBJECTIVES: Dental tissue-derived mesenchymal stem cells (MSCs)-mediated pulp-dentin regeneration is considered a potential approach for the regeneration of damaged teeth. Enhancing MSC-mediated pulp-dentin regeneration is based on an understanding of the molecular mechanisms underlying directed cell differentiation process. Histone demethylation enzyme, lysine demethylase 1A (KDM1A) can regulate the differentiation of some MSCs, but its role in dental tissue-derived MSCs is unclear. MATERIAL AND METHODS: We obtained SCAPs from immature teeth...
April 15, 2018: Cell Proliferation
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