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histone methylation

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https://www.readbyqxmd.com/read/29331887/idh1r132h-promotes-malignant-transformation-of-benign-prostatic-epithelium-by-dysregulating-micrornas-involvement-of-igf1r-akt-stat3-signaling-pathway
#1
Lili Zhang, Mei Qi, Tingting Feng, Jing Hu, Lin Wang, Xinjun Li, Wei Gao, Hui Liu, Meng Jiao, Zhen Wu, Xinnuo Bai, Yifan Bie, Long Liu, Bo Han
Risk stratification using molecular features could potentially help distinguish indolent from aggressive prostate cancer (PCa). Mutations in isocitrate dehydrogenase (IDH) acquire an abnormal enzymatic activity, resulting in the production of 2-hydroxyglutarate and alterations in cellular metabolism, histone modification, and DNA methylation. Mutant IDH1 has been identified in various human malignancies, and IDH1R132H constituted the vast majority of mutational events of IDH1. Most recent studies suggested that IDH1 mutations define a methylator subtype in PCa...
January 11, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29331452/design-synthesis-and-evaluation-of-%C3%AE-turn-mimetics-as-lsd1-selective-inhibitors
#2
Yosuke Ota, Shin Miyamura, Misaho Araki, Yukihiro Itoh, Shusuke Yasuda, Mitsuharu Masuda, Tomoyuki Taniguchi, Yoshihiro Sowa, Toshiyuki Sakai, Kenichiro Itami, Junichiro Yamaguchi, Takayoshi Suzuki
Lysine-specific demethylase 1 (LSD1) is an attractive molecular target for cancer therapy. We have previously reported potent LSD1-selective inhibitors (i.e., NCD18, NCD38, and their analogs) consisting of trans-2-phenylcyclopropylamine (PCPA) or trans-2-arylcyclopropylamine (ACPA) and a lysine moiety that could form a γ-turn structure in the active site of LSD1. Herein we report the design, synthesis and evaluation of γ-turn mimetic compounds for further improvement of LSD1 inhibitory activity and anticancer activity...
January 2, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29330124/manipulating-the-epigenome-for-the-treatment-of-disorders-with-thrombotic-complications
#3
REVIEW
Faith A A Kwa, Denise E Jackson
The haemostatic system is tightly regulated to maintain homeostasis to avoid unwanted bleeding or thrombotic complications. Recent research has highlighted the importance of epigenetic changes, such as DNA methylation, histone modifications, and miRNA-based mechanisms, that alter gene expression. This can give rise to dysregulated haemostatic or vascular expressed molecules contributing to the development of thrombotic complications. Targeting these epigenetic changes could provide a new avenue for the treatment of pathological blood clots...
January 9, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29330110/epigenetics-and-pathogenesis-of-systemic-sclerosis-the-ins-and-outs
#4
REVIEW
Saeed Aslani, Soheila Sobhani, Farhad Gharibdoost, Ahmadreza Jamshidi, Mahdi Mahmoudi
The pathogenesis of many diseases is influenced by environmental factors which can affect human genome and be inherited from generation to generation. Adverse environmental stimuli are recognized through the epigenetic regulatory complex, leading to gene expression alteration, which in turn culminates in disease outcomes. Three epigenetic regulatory mechanisms modulate the manifestation of a gene, namely DNA methylation, histone changes, and microRNAs. Both epigenetics and genetics have been implicated in the pathogenesis of systemic sclerosis (SSc) disease...
January 9, 2018: Human Immunology
https://www.readbyqxmd.com/read/29330049/the-histone-demethylase-phf8-promotes-adult-acute-lymphoblastic-leukemia-through-interaction-with-the-mek-erk-signaling-pathway
#5
Yue Fu, Yaling Yang, Xiaoming Wang, Xiaolin Yin, Minran Zhou, Siqi Wang, Lin Yang, Tao Huang, Man Xu, Chunyan Chen
Adult acute lymphoblastic leukemia (ALL) is a malignant disorder of lymphoid progenitor cells that is associated with a high risk of relapse and poor prognosis. Thus, novel pathogenic mechanisms and therapeutic targets need to be explored. Histone methylation is one of the most significant chromatin post-translational modifications. Here, we show that the histone demethylase PHF8 is highly expressed in a large number of ALL clinical specimens and that PHF8 expression is associated with ALL progression. PHF8 knockdown inhibits proliferation and promotes the apoptosis of ALL cells in vitro as well as attenuates tumor growth in vivo...
January 9, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29325932/riboflavin-attenuates-myocardial-injury-via-lsd1-mediated-crosstalk-between-phospholipid-metabolism-and-histone-methylation-in-mice-with-experimental-myocardial-infarction
#6
Peng Wang, Fan Fan, Xiao Li, Xiaolei Sun, Leilei Ma, Jian Wu, Cheng Shen, Hong Zhu, Zhen Dong, Cong Wang, Shuqi Zhang, Xiaona Zhao, Xin Ma, Yunzeng Zou, Kai Hu, Aijun Sun, Junbo Ge
The underlying mechanisms responsible for the cardioprotective effects of riboflavin remain elusive. Current study tested the hypothesis that riboflavin protects injured myocardium via epigenetic modification of LSD1. Here we showed that myocardial injury was attenuated and cardiac function was improved in riboflavin-treated mice with experimental myocardial infarction (MI), while these protective effects of riboflavin could be partly blocked by cotreatment with LSD1 inhibitor. Riboflavin also reduced apoptosis in hypoxic (1% oxygen) H9C2 cell lines...
January 8, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29325627/epigenetic-mechanisms-underlying-nervous-system-diseases
#7
Irfan A Qureshi, Mark F Mehler
Epigenetic mechanisms act as control systems for modulating genomic structure and activity in response to evolving profiles of cell-extrinsic, cell-cell, and cell-intrinsic signals. These dynamic processes are responsible for mediating cell- and tissue-specific gene expression and function and gene-gene and gene-environmental interactions. The major epigenetic mechanisms include DNA methylation and hydroxymethylation; histone protein posttranslational modifications, nucleosome remodeling/repositioning, and higher-order chromatin reorganization; noncoding RNA regulation; and RNA editing...
2018: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/29323282/mll2-conveys-transcription-independent-h3k4-trimethylation-in-oocytes
#8
Courtney W Hanna, Aaron Taudt, Jiahao Huang, Lenka Gahurova, Andrea Kranz, Simon Andrews, Wendy Dean, A Francis Stewart, Maria Colomé-Tatché, Gavin Kelsey
Histone 3 K4 trimethylation (depositing H3K4me3 marks) is typically associated with active promoters yet paradoxically occurs at untranscribed domains. Research to delineate the mechanisms of targeting H3K4 methyltransferases is ongoing. The oocyte provides an attractive system to investigate these mechanisms, because extensive H3K4me3 acquisition occurs in nondividing cells. We developed low-input chromatin immunoprecipitation to interrogate H3K4me3, H3K27ac and H3K27me3 marks throughout oogenesis. In nongrowing oocytes, H3K4me3 was restricted to active promoters, but as oogenesis progressed, H3K4me3 accumulated in a transcription-independent manner and was targeted to intergenic regions, putative enhancers and silent H3K27me3-marked promoters...
January 2018: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/29322246/de-novo-variants-in-setd1b-are-associated-with-intellectual-disability-epilepsy-and-autism
#9
Takuya Hiraide, Mitsuko Nakashima, Kaori Yamoto, Tokiko Fukuda, Mitsuhiro Kato, Hiroko Ikeda, Yoko Sugie, Kazushi Aoto, Tadashi Kaname, Kazuhiko Nakabayashi, Tsutomu Ogata, Naomichi Matsumoto, Hirotomo Saitsu
SETD1B (SET domain containing 1B) is a component of SET1 histone methyltransferase complex, which mediates the methylation of histone H3 on lysine 4 (H3K4). Here, we describe two unrelated individuals with de novo variants in SETD1B identified by trio-based whole exome sequencing: c.5524C>T, p.(Arg1842Trp) and c.5575C>T, p.(Arg1859Cy). The two missense variants occurred at evolutionarily conserved amino acids and are located within the SET domain, which plays a pivotal role in catalyzing histone methylation...
January 10, 2018: Human Genetics
https://www.readbyqxmd.com/read/29321829/dna-methylation-in-stroke-update-of-latest-advances
#10
REVIEW
Jerzy Krupinski, Caty Carrera, Elena Muiño, Nuria Torres, Raid Al-Baradie, Natalia Cullell, Israel Fernandez-Cadenas
Epigenetic modifications are hereditable and modifiable factors that do not alter the DNA sequence. These epigenetic factors include DNA methylation, acetylation of histones and non-coding RNAs. Epigenetic factors have mainly been associated with cancer but also with other diseases and conditions such as diabetes or obesity. In addition, epigenetic modifications could play an important role in cardiovascular diseases, including stroke. We review the latest advances in stroke epigenetics, focusing on DNA methylation studies and the future perspectives in this field...
2018: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/29321305/arabidopsis-rna-polymerase-v-mediates-enhanced-compaction-and-silencing-of-geminivirus-and-transposon-chromatin-during-host-recovery-from-infection
#11
Tami Coursey, Elizabeth Regedanz, David M Bisaro
Plants employ RNA-directed DNA methylation (RdDM) and dimethylation of histone 3 lysine 9 (H3K9me2) to silence geminiviruses and transposable elements (TEs). We previously showed that canonical RdDM (Pol IV-RdDM) involving RNA polymerases IV and V (Pol IV and Pol V) is required for Arabidopsis thaliana to recover from infection with Beet curly top virus lacking a suppressor protein that inhibits methylation (BCTV L2-). Recovery, which is characterized by reduced viral DNA levels and symptom remission, allows normal floral development...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321036/maternal-engineered-nanomaterial-inhalation-during-gestation-alters-the-fetal-transcriptome
#12
P A Stapleton, Q A Hathaway, C E Nichols, A B Abukabda, M V Pinti, D L Shepherd, C R McBride, J Yi, V C Castranova, J M Hollander, T R Nurkiewicz
BACKGROUND: The integration of engineered nanomaterials (ENM) is well-established and widespread in clinical, commercial, and domestic applications. Cardiovascular dysfunctions have been reported in adult populations after exposure to a variety of ENM. As the diversity of these exposures continues to increase, the fetal ramifications of maternal exposures have yet to be determined. We, and others, have explored the consequences of ENM inhalation during gestation and identified many cardiovascular and metabolic outcomes in the F1 generation...
January 10, 2018: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/29320873/does-progressive-nuclear-staining-with-hemalum-alum-hematoxylin-involve-dna-and-what-is-the-nature-of-the-dye-chromatin-complex
#13
J A Kiernan
Previous investigators have disagreed about whether hemalum stains DNA or its associated nucleoproteins. I review here the literature and describe new experiments in an attempt to resolve the controversy. Hemalum solutions, which contain aluminum ions and hematein, are routinely used to stain nuclei. A solution containing 16 Al3+ ions for each hematein molecule, at pH 2.0-2.5, provides selective progressive staining of chromatin without cytoplasmic or extracellular "background color." Such solutions contain a red cationic dye-metal complex and an excess of Al3+ ions...
January 11, 2018: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
https://www.readbyqxmd.com/read/29318979/role-of-epigenetics-and-oxidative-stress-in-gliomagenesis
#14
Edgar Rangel-Lopez, Yesennia Sanchez-Perez, Ernesto Soto-Reyes, Claudia Maria Garcia-Cuellar, Bernardo Cacho-Diaz, Abel Santamaria
Malignant gliomas constitute more than 49% of all central nervous system (CNS) tumors and exhibit very poor prognosis. Two main events involved with the progression of gliomas are the deregulation of genes by genetic events and cellular damage elicited by the formation of reactive oxygen species (ROS). In gliomas, epigenetic abnormalities implicated in the deregulation of DNA methylation, nucleosome rearrangement, and acetylation of histones have been depicted. The overproduction of ROS has been implicated in the promotion of these modifications...
January 10, 2018: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/29318497/epigenetic-mechanism-of-survivin-dysregulation-in-human-cancer
#15
REVIEW
Hui Lyu, Jingcao Huang, Zhimin He, Bolin Liu
Survivin (coding gene BIRC5) is a dual functional protein acting as a critical inhibitor of apoptosis (IAP) and key regulator of cell cycle progression. It is usually produced in embryonic tissues during development and undetectable in most adult tissues. Overexpression of Survivin frequently occurs in various human cancers and increased Survivin correlates with poor clinic outcome, tumor recurrence, and therapeutic resistance. Because of its selective expression in tumor, but not normal tissues, Survivin has been recognized as an attractive target for cancer treatment...
January 4, 2018: Science China. Life Sciences
https://www.readbyqxmd.com/read/29310839/decoding-colorectal-cancer-epigenomics
#16
REVIEW
Khalid El Bairi, Kanwal Tariq, Imane Himri, Abdeslam Jaafari, Wiam Smaili, Abdul Hafeez Kandhro, Adel Gouri, Bouchra Ghazi
Colorectal cancer (CRC) is very heterogeneous and presents different types of epigenetic alterations including DNA methylation, histone modifications and microRNAs. These changes are considered as characteristics of various observed clinical phenotypes. Undoubtedly, the discovery of epigenetic pathways with novel epigenetic-related mechanisms constitutes a promising advance in cancer biomarker discovery. In this review, we provide an evidence-based discussing of the current understanding of CRC epigenomics and its role in initiation, epithelial-to-mesenchymal transition and metastasis...
January 2018: Cancer Genetics
https://www.readbyqxmd.com/read/29310033/epigenetic-mechanisms-in-odontogenic-tumors-a-literature-review
#17
REVIEW
Jorge Sandoval-Basilio, Rogelio González-González, Ronell Bologna-Molina, Mario Isiordia-Espinoza, Gabriela Leija-Montoya, Sofia L Alcaraz-Estrada, Idanya Serafín-Higuera, Javier González-Ramírez, Nicolás Serafín-Higuera
OBJECTIVE: Epigenetic mechanisms, such as DNA methylation, regulate important biological processes as gene expression and it was suggested that these phenomena play important roles in the carcinogenesis and tumor biology. The aim of this review is to provide the current state of knowledge about epigenetic alterations, focusing mainly on DNA methylation, reported in odontogenic tumors. DESIGN: Literatures were searched based in the combination of the following keywords: odontogenic tumors, epigenetics, DNA methylation, histone modifications, non-coding RNA, microRNA, DNA methyltransferases...
December 30, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/29310022/loss-of-eed-leads-to-lineage-instability-and-increased-cd8-expression-of-mouse-cd4-t-cells-upon-tgf%C3%AE-signaling
#18
Taku Naito, Sawako Muroi, Ichiro Taniuchi, Motonari Kondo
Tri-methylation of lysine 27 on histone H3 (H3K27me3) is a repressive epigenetic modification catalyzed by polycomb repressive complex 2 (PRC2) that is required for proper cell fate determination as well as cellular function. Numerous studies have been performed to elucidate the role of PRC2 in T-cell differentiation and function; however, its role in the regulation of T-helper (Th) subset differentiation and identity has not been fully explored. Here, we report that Eed, an essential subunit of PRC2, is crucial to maintain the identity of CD4+ T cells under TGFβ-induced regulatory T cell (Treg)-polarizing conditions...
January 5, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29308692/maternal-obesity-diabetes-during-pregnancy-and-epigenetic-mechanisms-that-influence-the-developmental-origins-of-cardiometabolic-disease-in-the-offspring
#19
Prasoon Agarwal, Taylor S Morriseau, Stephanie M Kereliuk, Christine A Doucette, Brandy A Wicklow, Vernon W Dolinsky
Since 1980, global obesity has doubled, and the incidence of cardiometabolic diseases such as type 2 diabetes and heart disease is also increasing. While genetic susceptibility and adult lifestyle are implicated in these trends, evidence from clinical cohorts, epidemiological studies and animal model experiments support a role for early-life environmental exposures in determining the long-term health of an individual, which has led to the formulation of the Developmental Origins of Health and Disease (DOHaD) theory...
January 8, 2018: Critical Reviews in Clinical Laboratory Sciences
https://www.readbyqxmd.com/read/29308622/epigenetic-aberration-of-fmr1-gene-in-infertile-women-with-diminished-ovarian-reserve
#20
Hossein Eslami, Ali Eslami, Raha Favaedi, Ummolbanin Asadpour, Shabnam Zari Moradi, Poopak Eftekhari-Yazdi, Tahereh Madani, Maryam Shahhoseini, Anahita Mohseni Meybodi
OBJECTIVES: The diminished ovarian reserve (DOR) is a condition characterized by a reduction in the number and/or quality of oocytes. This primary infertility disorder is usually accompanied with an increase in the follicle-stimulating hormone (FSH) levels and regular menses. Although there are many factors contributing to the DOR situation, it is likely that many of idiopathic cases have genetic/epigenetic bases. The association between the FMR1 premutation (50-200 CGG repeats) and the premature ovarian failure (POF) suggests that epigenetic disorders of FMR1 can act as a risk factor for the DOR as well...
April 2018: Cell Journal
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