keyword
MENU ▼
Read by QxMD icon Read
search

Histone demethylases

keyword
https://www.readbyqxmd.com/read/28940624/alcohol-induced-behaviors-require-a-subset-of-drosophila-jmjc-domain-histone-demethylases-in-the-nervous-system
#1
Jorge H Pinzón, Addison R Reed, Nevine A Shalaby, Michael Buszczak, Aylin R Rodan, Adrian Rothenfluh
BACKGROUND: Long-lasting transcriptional changes underlie a number of adaptations that contribute to alcohol use disorders (AUD). Chromatin remodeling, including histone methylation, can confer distinct, long-lasting transcriptional changes, and histone methylases are known to play a role in the development of addiction. Conversely, little is known about the relevance of Jumonji (JmjC) domain-containing demethylases in AUDs. We systematically surveyed the alcohol-induced phenotypes of null mutations in all 13 Drosophila JmjC genes...
September 21, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28927255/innate-immune-response-of-bovine-mammary-epithelial-cells-to-mycoplasma-bovis
#2
Satoshi Gondaira, Hidetoshi Higuchi, Hidetomo Iwano, Koji Nishi, Takanori Nebu, Keiichi Nakajima, Hajime Nagahata
Mycoplasma species are contagious bacteria and Mycoplasma bovis mastitis is a serious productivity problem on dairy farms. Bovine mammary epithelial cells (bMEC) play an important role in the elimination of pathogens, but the effect of M. bovis on bMEC has not been fully clarified. To better understand the immune response against intramammary infection by M. bovis, we used microarray analysis to examine and profile mRNA expression in bMEC after stimulation with M. bovis. We also compared the effects of M. bovis, Staphylococcus aureus and Escherichia coli on immune-related mRNA expression in bMEC...
September 20, 2017: Journal of Veterinary Science
https://www.readbyqxmd.com/read/28926430/targeting-histone-methylation-in-cancer
#3
Michael T McCabe, Helai P Mohammad, Olena Barbash, Ryan G Kruger
Most, if not all, human cancers exhibit altered epigenetic signatures that promote aberrant gene expression that contributes to cellular transformation. Historically, attempts to pharmacologically intervene in this process have focused on DNA methylation and histone acetylation. More recently, genome-wide studies have identified histone and chromatin regulators as one of the most frequently dysregulated functional classes in a wide range of cancer types. These findings have provided numerous potential therapeutic targets including many that affect histone methylation...
September 2017: Cancer Journal
https://www.readbyqxmd.com/read/28905188/novel-inhibitors-of-lysine-k-specific-demethylase-4a-with-anticancer-activity
#4
Hyo Jeong Lee, Bo-Kyoung Kim, Kyoung Bin Yoon, Yong-Chul Kim, Sun-Young Han
Lysine (K)-specific demethylase 4A (KDM4A) is a histone demethylase that removes methyl residues from trimethylated or dimethylated histone 3 at lysines 9 and 36. Overexpression of KDM4A is found in various cancer types. To identify KDM4A inhibitors with anti-tumor functions, screening with an in vitro KDM4A enzyme activity assay was carried out. The benzylidenehydrazine analogue LDD2269 was selected, with an IC50 of 6.56 μM of KDM4A enzyme inhibition, and the binding mode was investigated using in silico molecular docking...
September 14, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28903624/repair-of-calvarial-bone-defect-using-jarid1a-knockdown-bone-mesenchymal-stem-cells-in-rats
#5
Yuan Deng, Tao Guo, Jipeng Li, Li Guo, Ping Gu, Xianqun Fan
Histone methylation is regarded as an important epigenetic event during stem cell differentiation. Jumonji AT-rich interactive domain 1A (Jarid1a) is a histone demethylase that specifically catalyzes demethylation of dimethyl or trimethyl histone H3K4me3, which is normally associated with transcriptionally active genes. Runt-related transcription factor 2 (Runx2) has been identified as a key transcription factor in the early stage of osteogenesis. A better understanding of this epigenetic mechanism that governs osteogenic differentiation of bone mesenchymal stem cells (BMSCs) can provide new insights into BMSCs based bone tissue engineering...
September 13, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28895234/runx2-induction-during-differentiation-of-wharton-s-jelly-mesenchymal-stem-cells-to-osteoblasts-is-regulated-by-jarid1b-histone-demethylase
#6
Francisco Bustos, Hugo Sepúlveda, Catalina P Prieto, Margarita Carrasco, Lorena Díaz, José Palma, José Lattus, Martín Montecino, Verónica Palma
Novel bone regeneration approaches aim to obtain immature osteoblasts from somatic stem cells. Umbilical cord Wharton's jelly mesenchymal stem cells (WJ-MSC) are an ideal source for cell therapy. Hence, the study of mechanisms involved in WJ-MSC osteoblastic differentiation is crucial to exploit their developmental capacity. Here, we have assessed epigenetic control of the RUNX2 osteogenic master regulator gene in WJ-MSC. We present evidence indicating that modulation of RUNX2 expression through preventing JARID1B histone demethylase activity is relevant to enhance WJ-MSC osteoblastic potential...
September 12, 2017: Stem Cells
https://www.readbyqxmd.com/read/28894299/dhea-inhibits-acute-microglia-mediated-inflammation-through-activation-of-the-trka-akt1-2-creb-jmjd3-pathway
#7
V I Alexaki, G Fodelianaki, A Neuwirth, C Mund, A Kourgiantaki, E Ieronimaki, K Lyroni, M Troullinaki, C Fujii, W Kanczkowski, A Ziogas, M Peitzsch, S Grossklaus, B Sönnichsen, A Gravanis, S R Bornstein, I Charalampopoulos, C Tsatsanis, T Chavakis
Dehydroepiandrosterone (DHEA) is the most abundant circulating steroid hormone in humans, produced by the adrenals, the gonads and the brain. DHEA was previously shown to bind to the nerve growth factor receptor, tropomyosin-related kinase A (TrkA), and to thereby exert neuroprotective effects. Here we show that DHEA reduces microglia-mediated inflammation in an acute lipopolysaccharide-induced neuro-inflammation model in mice and in cultured microglia in vitro. DHEA regulates microglial inflammatory responses through phosphorylation of TrkA and subsequent activation of a pathway involving Akt1/Akt2 and cAMP response element-binding protein...
September 12, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28894274/kdm4a-regulates-hif-1-levels-through-h3k9me3
#8
Grzegorz Dobrynin, Tom E McAllister, Katarzyna B Leszczynska, Shaliny Ramachandran, Adam J Krieg, Akane Kawamura, Ester M Hammond
Regions of hypoxia (low oxygen) occur in most solid tumours and cells in these areas are the most aggressive and therapy resistant. In response to decreased oxygen, extensive changes in gene expression mediated by Hypoxia-Inducible Factors (HIFs) contribute significantly to the aggressive hypoxic tumour phenotype. In addition to HIFs, multiple histone demethylases are altered in their expression and activity, providing a secondary mechanism to extend the hypoxic signalling response. In this study, we demonstrate that the levels of HIF-1α are directly controlled by the repressive chromatin mark, H3K9me3...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28892104/synergistic-anti-aml-effects-of-the-lsd1-inhibitor-t-3775440-and-the-nedd8-activating-enzyme-inhibitor-pevonedistat-via-transdifferentiation-and-dna-rereplication
#9
Y Ishikawa, K Nakayama, M Morimoto, A Mizutani, A Nakayama, K Toyoshima, A Hayashi, S Takagi, R Dairiki, H Miyashita, S Matsumoto, K Gamo, T Nomura, K Nakamura
Lysine-specific demethylase 1A (LSD1, KDM1A) specifically demethylates di- and monomethylated histones H3K4 and K9, resulting in context-dependent transcriptional repression or activation. We previously identified an irreversible LSD1 inhibitor T-3775440, which exerts antileukemic activities in a subset of acute myeloid leukemia (AML) cell lines by inducing cell transdifferentiation. The NEDD8-activating enzyme inhibitor pevonedistat (MLN4924, TAK-924) is an investigational drug with antiproliferative activities in AML, and is also reported to induce cell differentiation...
September 11, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28890349/molecular-hydrogen-modulates-gene-expression-via-histone-modification-and-induces-the-mitochondrial-unfolded-protein-response
#10
Sayaka Sobue, Chisato Inoue, Fumiko Hori, Shanlou Qiao, Takashi Murate, Masatoshi Ichihara
Molecular hydrogen (H2) is a biologically active gas that is used medically to ameliorate various systemic pathological conditions. H2 also regulates gene expression involved in intracellular signaling and metabolic pathways. However, it is unclear whether H2 affects gene expression directly or through indirect effects as a consequence of health improvement. Therefore, we attempted to identify genes that exhibit similar changes in expression in response to H2 by employing DNA microarrays and gene set enrichment analysis to analyze RNA from liver and lung of rats and mice with or without dietary stress...
September 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28889393/epigenetic-treatment-options-in-urothelial-carcinoma
#11
Maria Pinkerneil, Michèle J Hoffmann, Günter Niegisch
Mutations, dysregulation, and dysbalance of epigenetic regulators are especially frequent in urothelial carcinoma (UC) compared to other malignancies. Accordingly, targeting epigenetic regulators may provide a window of opportunity particularly in anticancer therapy of UC. In general, these epigenetic regulators comprise DNA methyltransferases and DNA demethylases (for DNA methylation), histone methyltransferases, and histone demethylases (for histone methylation) as well as acetyl transferases and histone deacetylases (for histone and non-histone acetylation)...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28880717/bivalent-histone-codes-on-wnt5a-during-odontogenic-differentiation
#12
Y Zhou, L Zheng, F Li, M Wan, Y Fan, X Zhou, W Du, C Pi, D Cui, B Zhang, J Sun, X Zhou
Lineage-committed differentiation is an essential biological program during odontogenesis, which is tightly regulated by lineage-specific genes. Some of these genes are modified by colocalization of H3K4me3 and H3K27me3 marks at promoter regions in progenitors. These modifications, named "bivalent domains," maintain genes in a poised state and then resolve for later activation or repression during differentiation. Wnt5a has been reported to promote odontogenic differentiation in dental mesenchyme. However, relatively little is known about the epigenetic modulations on Wnt5a activation during tooth development...
September 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28878246/loss-of-nr2e3-represses-ahr-by-lsd1-reprogramming-is-associated-with-poor-prognosis-in-liver-cancer
#13
Tilak Khanal, Kwangmin Choi, Yuet-Kin Leung, Jiang Wang, Dasom Kim, Vinothini Janakiram, Sung-Gook Cho, Alvaro Puga, Shuk-Mei Ho, Kyounghyun Kim
The aryl hydrocarbon receptor (AHR) plays crucial roles in inflammation, metabolic disorder, and cancer. However, the molecular mechanisms regulating AHR expression remain unknown. Here, we found that an orphan nuclear NR2E3 maintains AHR expression, and forms an active transcriptional complex with transcription factor Sp1 and coactivator GRIP1 in MCF-7 human breast and HepG2 liver cancer cell lines. NR2E3 loss promotes the recruitment of LSD1, a histone demethylase of histone 3 lysine 4 di-methylation (H3K4me2), to the AHR gene promoter region, resulting in repression of AHR expression...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28867287/dynamic-control-of-x-chromosome-conformation-and-repression-by-a-histone-h4k20-demethylase
#14
Katjuša Brejc, Qian Bian, Satoru Uzawa, Bayly S Wheeler, Erika C Anderson, David S King, Philip J Kranzusch, Christine G Preston, Barbara J Meyer
Chromatin modification and higher-order chromosome structure play key roles in gene regulation, but their functional interplay in controlling gene expression is elusive. We have discovered the machinery and mechanism underlying the dynamic enrichment of histone modification H4K20me1 on hermaphrodite X chromosomes during C. elegans dosage compensation and demonstrated H4K20me1's pivotal role in regulating higher-order chromosome structure and X-chromosome-wide gene expression. The structure and the activity of the dosage compensation complex (DCC) subunit DPY-21 define a Jumonji demethylase subfamily that converts H4K20me2 to H4K20me1 in worms and mammals...
September 21, 2017: Cell
https://www.readbyqxmd.com/read/28855511/blood-monocyte-transcriptome-and-epigenome-analyses-reveal-loci-associated-with-human-atherosclerosis
#15
Yongmei Liu, Lindsay M Reynolds, Jingzhong Ding, Li Hou, Kurt Lohman, Tracey Young, Wei Cui, Zhiqing Huang, Carole Grenier, Ma Wan, Hendrik G Stunnenberg, David Siscovick, Lifang Hou, Bruce M Psaty, Stephen S Rich, Jerome I Rotter, Joel D Kaufman, Gregory L Burke, Susan Murphy, David R Jacobs, Wendy Post, Ina Hoeschele, Douglas A Bell, David Herrington, John S Parks, Russell P Tracy, Charles E McCall, James H Stein
Little is known regarding the epigenetic basis of atherosclerosis. Here we present the CD14+ blood monocyte transcriptome and epigenome signatures associated with human atherosclerosis. The transcriptome signature includes transcription coactivator, ARID5B, which is known to form a chromatin derepressor complex with a histone H3K9Me2-specific demethylase and promote adipogenesis and smooth muscle development. ARID5B CpG (cg25953130) methylation is inversely associated with both ARID5B expression and atherosclerosis, consistent with this CpG residing in an ARID5B enhancer region, based on chromatin capture and histone marks data...
August 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/28843785/hif-1%C3%AE-coordinates-epigenetic-activation-of-siah1-in-hepatocytes-in-response-to-nutritional-stress
#16
Zhiwen Fan, Zilong Li, Yuyu Yang, Shuai Liu, Junli Guo, Yong Xu
Hypoxia inducible factor 1 alpha (HIF-1α) regulates a diverse range of pathophysiological processes. It has been demonstrated previously that HIF-1α plays a role in the pathogenesis of steatosis mediating the effects of excessive nutritional insults. In the present study we investigated the role of HIF-1α in trans‑activating the seven in absentia homolog 1 (SIAH1) gene and the underlying mechanism. We report that in response to nutritional stress, SIAH1 expression was up-regulated in the liver in mice and in cultured hepatocytes...
August 24, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28838216/bet-inhibitors-a-novel-epigenetic-approach
#17
D B Doroshow, J P Eder, P M LoRusso
Epigenetics has been defined as 'the structural adaptation of chromosomal regions so as to register, signal or perpetuate altered activity states.' Currently, several classes of anticancer drugs function at the epigenetic level, including inhibitors of DNA methyltransferase, histone deacetylase (HDAC), lysine-specific demethylase 1, zeste homolog 2, and bromodomain and extra-terminal motif (BET) proteins.BET proteins have multiple functions, including the initiation and elongation of transcription and cell cycle regulation...
August 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28835804/design-of-kdm4-inhibitors-with-antiproliferative-effects-in-cancer-models
#18
Young K Chen, Tiziana Bonaldi, Alessandro Cuomo, Joselyn R Del Rosario, David J Hosfield, Toufike Kanouni, Shih-Chu Kao, Chon Lai, Neethan A Lobo, Jennifer Matuszkiewicz, Andrew McGeehan, Shawn M O'Connell, Lihong Shi, Jeffrey A Stafford, Ryan K Stansfield, James M Veal, Michael S Weiss, Natalie Y Yuen, Michael B Wallace
Histone lysine demethylases (KDMs) play a vital role in the regulation of chromatin-related processes. Herein, we describe our discovery of a series of potent KDM4 inhibitors that are both cell permeable and antiproliferative in cancer models. The modulation of histone H3K9me3 and H3K36me3 upon compound treatment was verified by homogeneous time-resolved fluorescence assay and by mass spectroscopy detection. Optimization of the series using structure-based drug design led to compound 6 (QC6352), a potent KDM4 family inhibitor that is efficacious in breast and colon cancer PDX models...
August 10, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28832116/chemically-sumoylated-histone-h4-stimulates-intranucleosomal-demethylation-by-the-lsd1-corest-complex
#19
Abhinav Dhall, Caroline E Weller, Aurea Chu, Patrick M M Shelton, Champak Chatterjee
Lysine-specific demethylase 1 (LSD1) downregulates eukaryotic gene activity by demethylating mono- and dimethylated Lys4 in histone H3. Elucidating the biochemical crosstalk of LSD1 with histone post-translational modifications (PTMs) is essential for developing LSD1-targeted therapeutics in human cancers. We interrogated the small ubiquitin-like modifier (SUMO)-driven regulation of LSD1 activity with semisynthetic nucleosomes containing site-specifically methylated and sumoylated histones. We discovered that nucleosomes containing sumoylated histone H4 (suH4), a modification associated with gene repression, stimulate LSD1 activity by a mechanism dependent upon the SUMO-interaction motif in CoREST...
August 30, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28827393/maternal-expression-of-the-jmjd2a-kdm4a-histone-demethylase-is-critical-for-pre-implantation-development
#20
Aditya Sankar, Susanne Marije Kooistra, Javier Martin Gonzalez, Claes Ohlsson, Matti Poutanen, Kristian Helin
Regulation of chromatin composition through post-translational modifications of histones contributes to transcriptional regulation and is essential for many cellular processes, including differentiation and development. JMJD2A/KDM4A is a lysine demethylase with specificity towards di- and tri-methylated lysine 9 and lysine 36 of histone H3 (H3K9me2/me3 and H3K36me2/me3). Here, we report that Kdm4a as a maternal factor plays a key role in embryo survival and is vital for female fertility. Kdm4a(-/-) female mice ovulate normally with comparable fertilization but poor implantation rates, and cannot support healthy transplanted embryos to term...
August 21, 2017: Development
keyword
keyword
66344
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"