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Histone H4

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https://www.readbyqxmd.com/read/29786745/histone-modifications-in-fatty-acid-synthase-modulated-by-carbohydrate-responsive-element-binding-protein-are-associated-with-non%C3%A2-alcoholic-fatty-liver-disease
#1
Can Cai, Huihong Yu, Guangming Huang, Xuan Du, Xiaoqing Yu, Youping Zhou, Wei Shen
Non‑alcoholic fatty liver disease (NAFLD) is a manifestation of metabolic syndrome in the liver and is closely associated with diabetes; however, its pathogenesis remains to be elucidated. Carbohydrate responsive element binding protein (ChREBP), the hub of glucolipid metabolism, regulates the induction of fatty acid synthase (FASN), the key enzyme of de novo lipogenesis, by directly binding to carbohydrate response element (ChoRE) in its promoter. Investigations of histone modifications on NAFLD remain in their infancy...
May 22, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29778792/valproic-acid-attenuates-manganese-induced-reduction-in-expression-of-glt-1-and-glast-with-concomitant-changes-in-murine-dopaminergic-neurotoxicity
#2
James Johnson, Edward Pajarillo, Pratap Karki, Judong Kim, Deok-Soo Son, Michael Aschner, Eunsook Lee
Exposure to elevated levels of manganese (Mn) causes manganism, a neurological disorder with similar characteristics to those of Parkinson's disease (PD). Valproic acid (VPA), an antiepileptic, is known to inhibit histone deacetylases and exert neuroprotective effects in many experimental models of neurological disorders. In the present study, we investigated if VPA attenuated Mn-induced dopaminergic neurotoxicity and the possible mechanisms involved in VPA's neuroprotection, focusing on modulation of astrocytic glutamate transporters (glutamate aspartate transporter, GLAST and glutamate transporter 1, GLT-1) and histone acetylation in H4 astrocyte culture and mouse models...
May 17, 2018: Neurotoxicology
https://www.readbyqxmd.com/read/29778644/a-trichostatin-a-tsa-sp1-mediated-mechanism-for-the-regulation-of-sall2-tumor-suppressor-in-jurkat-t-cells
#3
Matías I Hepp, David Escobar, Carlos Farkas, Viviana Hermosilla, Claudia Álvarez, Roberto Amigo, José L Gutiérrez, Ariel F Castro, Roxana Pincheira
SALL2 is a transcription factor involved in development and disease. Deregulation of SALL2 has been associated with cancer, suggesting that it plays a role in the disease. However, how SALL2 is regulated and why is deregulated in cancer remain poorly understood. We previously showed that the p53 tumor suppressor represses SALL2 under acute genotoxic stress. Here, we investigated the effect of Histone Deacetylase Inhibitor (HDACi) Trichostatin A (TSA), and involvement of Sp1 on expression and function of SALL2 in Jurkat T cells...
May 17, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29776834/bet-bromodomain-ligands-probing-the-wpf-shelf-to-improve-brd4-bromodomain-affinity-and-metabolic-stability
#4
Laura E Jennings, Matthias Schiedel, David S Hewings, Sarah Picaud, Corentine M C Laurin, Paul A Bruno, Joseph P Bluck, Amy R Scorah, Larissa See, Jessica K Reynolds, Mustafa Moroglu, Ishna N Mistry, Amy Hicks, Pavel Guzanov, James Clayton, Charles N G Evans, Giulia Stazi, Philip C Biggin, Anna K Mapp, Ester M Hammond, Philip G Humphreys, Panagis Filippakopoulos, Stuart J Conway
Ligands for the bromodomain and extra-terminal domain (BET) family of bromodomains have shown promise as useful therapeutic agents for treating a range of cancers and inflammation. Here we report that our previously developed 3,5-dimethylisoxazole-based BET bromodomain ligand (OXFBD02) inhibits interactions of BRD4(1) with the RelA subunit of NF-κB, in addition to histone H4. This ligand shows a promising profile in a screen of the NCI-60 panel but was rapidly metabolised (t½  = 39.8 min). Structure-guided optimisation of compound properties led to the development of the 3-pyridyl-derived OXFBD04...
May 15, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29776409/calcitriol-downregulates-fibroblast-growth-factor-receptor-1-through-histone-deacetylase-activation-in-hl-1-atrial-myocytes
#5
Ting-Wei Lee, Ting-I Lee, Yung-Kuo Lin, Yu-Hsun Kao, Yi-Jen Chen
BACKGROUND: Fibroblast growth factor (FGF)-2 plays a crucial role in the pathophysiology of cardiovascular diseases (CVDs). FGF-2 was reported to induce cardiac hypertrophy through activation of FGF receptor 1 (FGFR1). Multiple laboratory findings indicate that calcitriol may be a potential treatment for CVDs. In this study, we attempted to investigate whether calcitriol regulates FGFR1 expression to modulate the effects of FGF-2 signaling in cardiac myocytes and explored the potential regulatory mechanism...
May 18, 2018: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29775289/mass-spectral-detection-of-diethoxyphospho-tyrosine-adducts-on-proteins-from-hek293-cells-using-monoclonal-antibody-depy-for-enrichment
#6
Seda Onder, Lawrence M Schopfer, Ozden Tacal, Thomas A Blake, Rudolph C Johnson, Oksana Lockridge
Chronic illness from exposure to organophosphorus toxicants is hypothesized to involve modification of unknown proteins. Tyrosine in proteins that have no active site serine readily reacts with organophosphorus toxicants. We developed a monoclonal antibody, depY, that specifically recognizes diethoxyphospho-tyrosine in proteins and peptides, independent of the surrounding amino acid sequence. Our goal in the current study was to identify diethoxyphosphorylated proteins in human HEK293 cell lysate treated with chlorpyrifos oxon...
May 18, 2018: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29774413/alterations-in-histone-acetylation-following-exposure-to-60-co-%C3%AE-rays-and-their-relationship-with-chromosome-damage-in-human-lymphoblastoid-cells
#7
Xue-Lei Tian, Xue Lu, Jiang-Bin Feng, Tian-Jing Cai, Shuang Li, Mei Tian, Qing-Jie Liu
Chromosome damage is related to DNA damage and erroneous repair. It can cause cell dysfunction and ultimately induce carcinogenesis. Histone acetylation is crucial for regulating chromatin structure and DNA damage repair. Ionizing radiation (IR) can alter histone acetylation. However, variations in histone acetylation in response to IR exposure and the relationship between histone acetylation and IR-induced chromosome damage remains unclear. Hence, this study investigated the variation in the total acetylation levels of H3 and H4 in human lymphocytes exposed to 0-2 Gy 60 Co γ-rays...
May 17, 2018: Radiation and Environmental Biophysics
https://www.readbyqxmd.com/read/29773913/auxin-decreases-chromatin-accessibility-through-the-tir1-afbs-auxin-signaling-pathway-in-proliferative-cells
#8
Junko Hasegawa, Takuya Sakamoto, Satoru Fujimoto, Tomoe Yamashita, Takamasa Suzuki, Sachihiro Matsunaga
Chromatin accessibility is closely associated with chromatin functions such as gene expression, DNA replication, and maintenance of DNA integrity. However, the relationship between chromatin accessibility and plant hormone signaling has remained elusive. Here, based on the correlation between chromatin accessibility and DNA damage, we used the sensitivity to DNA double strand breaks (DSBs) as an indicator of chromatin accessibility and demonstrated that auxin regulates chromatin accessibility through the TIR1/AFBs signaling pathway in proliferative cells...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29764934/structure-specific-recognition-protein-1-ssrp1-is-an-elongated-homodimer-that-binds-histones
#9
Gabriele Marcianò, Stefano Da Vela, Giancarlo Tria, Dmitri I Svergun, Olwyn Byron, Danny T Huang
The histone chaperone complex facilitates chromatin transcription (FACT) plays important roles in DNA repair, replication, and transcription. In the formation of this complex, structure-specific recognition protein-1 (SSRP1) heterodimerizes with suppressor of Ty 16 (SPT16). SSRP1 also has SPT16-independent functions, but how SSRP1 functions alone remains elusive. Here, using analytical ultracentrifugation (AUC) and small-angle X-ray scattering (SAXS) techniques, we characterized human SSRP1 and that from the amoeba Dictyostelium discoideum and show that both orthologs form an elongated homodimer in solution...
May 15, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29762370/molecular-regulations-of-mucosal-maltase-expressions
#10
Toshinao Goda, Kazue Honma
Two major α-glucosidase (maltase) genes, sucrase-isomaltase (SI) and maltase-glucoamylase (MGAM), respectively, are expressed in the small intestine. In this review, we have summarized whether jejunal expression of these maltase genes is regulated by dietary manipulations, which may affect carbohydrate availability from the luminal side, through changes in the binding of transcription factors and/or histone code on these genes. Studies using a model of mice fed either a low-starch or a high-starch diet for 7 days, found the mRNA levels of SI, MGAM, and Na-glucose cotransporter (SGLT1) genes in the jejunum to be increased in parallel by feeding a high-starch diet...
June 2018: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/29752310/extracellular-histones-inhibit-complement-activation-through-interacting-with-complement-component-4
#11
Yasir Qaddoori, Simon T Abrams, Paul Mould, Yasir Alhamdi, Stephen E Christmas, Guozheng Wang, Cheng-Hock Toh
Complement activation leads to membrane attack complex formation, which can lyse not only pathogens but also host cells. Histones can be released from the lysed or damaged cells and serve as a major type of damage-associated molecular pattern, but their effects on the complement system are not clear. In this study, we pulled down two major proteins from human serum using histone-conjugated beads: one was C-reactive protein and the other was C4, as identified by mass spectrometry. In surface plasmon resonance analysis, histone H3 and H4 showed stronger binding to C4 than other histones, with KD around 1 nM...
May 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29751847/asf1-is-required-to-load-histones-on-the-hira-complex-in-preparation-of-paternal-chromatin-assembly-at-fertilization
#12
Béatrice Horard, Laure Sapey-Triomphe, Emilie Bonnefoy, Benjamin Loppin
BACKGROUND: Anti-Silencing Factor 1 (ASF1) is a conserved H3-H4 histone chaperone involved in both Replication-Coupled and Replication-Independent (RI) nucleosome assembly pathways. At DNA replication forks, ASF1 plays an important role in regulating the supply of H3.1/2 and H4 to the CAF-1 chromatin assembly complex. ASF1 also provides H3.3-H4 dimers to HIRA and DAXX chaperones for RI nucleosome assembly. The early Drosophila embryo is an attractive system to study chromatin assembly in a developmental context...
May 11, 2018: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29745061/middle-down-ms-is-ready-to-answer-complex-questions-in-chromatin-biology
#13
Simone Sidoli
Histones are the most abundant protein family in the cells of complex organisms such as mammals and, together with DNA, they define the backbone of chromatin. Histone PTMs are key players of chromatin biology, as they function as anchors for proteins that bind and modulate chromatin readout, including gene expression. Middle-down mass spectrometry (MS) has been optimized for about 10 years to study histone N-terminal tails, but it has been rarely applied to identify the role of co-existing histone marks in biology...
May 9, 2018: Proteomics
https://www.readbyqxmd.com/read/29742153/identification-of-a-peptide-inhibitor-for-the-histone-methyltransferase-whsc1
#14
Michael J Morrison, P Ann Boriack-Sjodin, Kerren K Swinger, Tim J Wigle, Dipti Sadalge, Kevin W Kuntz, Margaret Porter Scott, William P Janzen, Richard Chesworth, Kenneth W Duncan, Darren M Harvey, John W Lampe, Lorna H Mitchell, Robert A Copeland
WHSC1 is a histone methyltransferase that is responsible for mono- and dimethylation of lysine 36 on histone H3 and has been implicated as a driver in a variety of hematological and solid tumors. Currently, there is a complete lack of validated chemical matter for this important drug discovery target. Herein we report on the first fully validated WHSC1 inhibitor, PTD2, a norleucine-containing peptide derived from the histone H4 sequence. This peptide exhibits micromolar affinity towards WHSC1 in biochemical and biophysical assays...
2018: PloS One
https://www.readbyqxmd.com/read/29729078/archaeal-dna-on-the-histone-merry-go-round
#15
Sudipta Bhattacharyya, Francesca Mattiroli, Karolin Luger
How did the nucleosome, the fundamental building block of all eukaryotic chromatin, evolve? This central question has been impossible to address because the four core histones that make up the protein core of the nucleosome are so highly conserved in all eukaryotes. With the discovery of small, minimalist histone-like proteins in most known archaea, the likely origin of histones was identified. We recently determined the structure of an archaeal histone-DNA complex, revealing that archaeal DNA topology and protein-DNA interactions are astonishingly similar compared to the eukaryotic nucleosome...
May 4, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29721093/graphene-oxide-sensitizes-cancer-cells-to-chemotherapeutics-by-inducing-early-autophagy-events-promoting-nuclear-trafficking-and-necrosis
#16
Kuan-Chen Lin, Mei-Wei Lin, Mu-Nung Hsu, Guan Yu-Chen, Yu-Chan Chao, Hsing-Yu Tuan, Chi-Shiun Chiang, Yu-Chen Hu
Rationale: Cisplatin (CDDP) is a broad-spectrum anticancer drug but chemoresistance to CDDP impedes its wide use for cancer therapy. Autophagy is an event occurring in the cytoplasm and cytoplasmic LC3 puncta formation is a hallmark of autophagy. Graphene oxide (GO) is a nanomaterial that provokes autophagy in CT26 colon cancer cells and confers antitumor effects. Here we aimed to evaluate whether combined use of GO with CDDP (GO/CDDP) overcomes chemoresistance in different cancer cells and uncover the underlying mechanism...
2018: Theranostics
https://www.readbyqxmd.com/read/29719500/valproic-acid-attenuates-traumatic-brain-injury-induced-inflammation-in-vivo-involvement-of-autophagy-and-the-nrf2-are-signaling-pathway
#17
Xiangrong Chen, Handong Wang, Mengliang Zhou, Xiang Li, Zhongning Fang, Hongzhi Gao, Yasong Li, Weipeng Hu
Microglial activation and the inflammatory response in the central nervous system (CNS) play important roles in secondary damage after traumatic brain injury (TBI). Transcriptional activation of genes that limit secondary damage to the CNS are mediated by a cis-acting element called the antioxidant responsive element (ARE). ARE is known to associate with the transcription factor NF-E2-related factor 2 (Nrf2), a transcription factor that is associated with histone deacetylases (HDACs). This pathway, known as the Nrf2/ARE pathway, is a critical antioxidative factor pathway that regulates the balance of oxygen free radicals and the inflammatory response, and is also related to autophagic activities...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29715476/epigenetic-upregulation-of-cxcl12-expression-contributes-to-the-acquisition-and-maintenance-of-morphine-induced-conditioned-place-preference
#18
Huan Liu, Jiayou Wei, Meng Liu, Shaoling Wu, Chao Ma, Cuicui Liu, Kangmei Huang, Xueqin Zhang, Ruixian Guo, Kuibo Zhang, Wenjun Xin
Addiction and rewarding effect is a primary side effect of morphine, which is commonly used to relieve the acute or chronic pain. Several lines of evidence have suggested that inflammation response in the VTA contributes to morphine-induced reward (conditioned place preference, CPP), while the mechanism are poorly understood. The present study showed that repeated morphine conditioning persistently increased the expression of CXCL12 mRNA and protein in VTA. Furthermore, inhibition of CXCL12 prevented the acquisition and maintenance, but not the expression, of morphine-induced CPP in rodent...
April 30, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29704439/histone-deacetylase-inhibitor-chidamide-promotes-reactivation-of-latent-hiv-by-introducing-histone-acetylation
#19
Qiyuan Kuai, Xiaofan Lu, Zhixin Qiao, Rui Wang, Yanbing Wang, Sanxian Ye, Min He, Yu Wang, Tong Zhang, Hao Wu, Suping Ren, Qun Yu
Highly active antiretroviral therapy (HAART) can reduce the HIV viral load in the plasma to undetectable levels. However, due to the presence of latent HIV reservoirs, it is difficult to completely eradicate HIV in infected patients. Our objective was to assess the potency of chidamide, a novel histone deacetylase inhibitor (HDACi) recently approved for cancer treatment by the China Food and Drug Administration (CFDA), to reactivate latent HIV-1 via histone acetylation. Viral reactivities of chidamide were accessed in two latent HIV pseudotype virus cell reporter systems (J-Lat Tat-GFP Clone A72 and TZM-bl), a latently infected full-length HIV virus cell system (U1/HIV), and resting CD4+ T cells from nine HIV-infected patients under HAART with undetectable viral load...
April 28, 2018: Journal of Medical Virology
https://www.readbyqxmd.com/read/29704392/the-nephroprotective-effect-of-ms-275-on-lipopolysaccharide-lps-induced-acute-kidney-injury-by-inhibiting-reactive-oxygen-species-ros-oxidative-stress-and-endoplasmic-reticulum-stress
#20
Haiyue Zhang, Wenbin Zhang, Fangzhou Jiao, Xun Li, Hong Zhang, Luwen Wang, Zuojiong Gong
BACKGROUND Histone deacetylase (HDAC) inhibitors can attenuate acute kidney injury (AKI)-mediated damage and reduce fibrosis in kidney disease models. The aim of the present study was to investigate the effects of the HDAC inhibitor MS-275 on lipopolysaccharide (LPS)-induced AKI and the associated mechanisms. MATERIAL AND METHODS A LPS-induced model in 6-8 weeks-old mice was established by intraperitoneal injection of LPS (10 mg/kg), with pre-treatment of MS-275 (2 mg/kg/day) administered intraperitoneally for five days...
April 28, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
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