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Histone H4

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https://www.readbyqxmd.com/read/28815970/structural-insight-into-cbp-bromodomain-mediated-recognition-of-acetylated-histone-h3k56ac
#1
Li Xu, Aimin Cheng, Min Huang, Jiahai Zhang, Yiyang Jiang, Chongyuan Wang, Fudong Li, Hongyu Bao, Jia Gao, Na Wang, Jiuyang Liu, Jihui Wu, Catherine C L Wong, Ke Ruan
The acetylation of lysine 56 of histone H3 (H3K56ac) enhances the binding affinity of histone chaperones to H3-H4 dimers. CREB binding protein (CBP) possesses a bromodomain that recognizes H3K56 acetylation. CBP also possesses a histone acetyltransferase (HAT) domain, which has been shown to promote H3K56 acetylation of free histones to facilitate delivery of replication-dependent chaperones to acetylated histones for chromatin assembly. However, the mechanism by which the CBP bromodomain recognizes H3K56ac, and thecontext in which such recognition occurs remains elusive...
August 16, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28813589/regulation-of-stability-on-histone-h2a-h2b-dimer-by-h2a-tyr57-phosphorylation
#2
Takuma Sueoka, Gosuke Hayashi, Akimitsu Okamoto
Histone H2A and H2B form a H2A-H2B heterodimer, which is a fundamental unit of nucleosome assembly and disassembly. Several posttranslational modifications change the interface between the H2A-H2B dimer and the H3-H4 tetramer, and regulate nucleosome stability. However, posttranslational modifications associated with the interface between H2A and H2B have not been discussed. In this paper, it is shown that Tyr57 phosphorylation in H2A strongly influences H2A-H2B dimerization. Tyr57-phosphorylated H2A was chemically synthesized and utilized to reconstitute the H2A-H2B dimer and nucleosome as well as canonical H2A...
August 16, 2017: Biochemistry
https://www.readbyqxmd.com/read/28811661/myst2-kat7-histone-acetyltransferase-interaction-proteomics-reveals-tumour-suppressor-niam-as-a-novel-binding-partner-in-embryonic-stem-cells
#3
Mercedes Pardo, Lu Yu, Shihpei Shen, Peri Tate, Daniel Bode, Blake L Letney, Dawn E Quelle, William Skarnes, Jyoti S Choudhary
MYST histone acetyltransferases have crucial functions in transcription, replication and DNA repair and are hence implicated in development and cancer. Here we characterise Myst2/Kat7/Hbo1 protein interactions in mouse embryonic stem cells by affinity purification coupled to mass spectrometry. This study confirms that in embryonic stem cells Myst2 is part of H3 and H4 histone acetylation complexes similar to those described in somatic cells. We identify a novel Myst2-associated protein, the tumour suppressor protein Niam (Nuclear Interactor of ARF and Mdm2)...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811569/transcriptional-response-to-stress-is-pre-wired-by-promoter-and-enhancer-architecture
#4
Anniina Vihervaara, Dig Bijay Mahat, Michael J Guertin, Tinyi Chu, Charles G Danko, John T Lis, Lea Sistonen
Programs of gene expression are executed by a battery of transcription factors that coordinate divergent transcription from a pair of tightly linked core initiation regions of promoters and enhancers. Here, to investigate how divergent transcription is reprogrammed upon stress, we measured nascent RNA synthesis at nucleotide-resolution, and profiled histone H4 acetylation in human cells. Our results globally show that the release of promoter-proximal paused RNA polymerase into elongation functions as a critical switch at which a gene's response to stress is determined...
August 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28802016/involvement-of-sperm-acetylated-histones-and-the-nuclear-isoform-of-glutathione-peroxidase-4-in-fertilization
#5
Simona Pipolo, Rossella Puglisi, Valentina Mularoni, Valentina Esposito, Andrea Fuso, Marco Lucarelli, Maria Teresa Fiorenza, Franco Mangia, Carla Boitani
We previously demonstrated that the nuclear form of Glutathione Peroxidase 4 (nGPx4) has a peculiar distribution in sperm head, being localized to nuclear matrix and acrosome and that sperm lacking nGPx4 are more prone to decondensation in vitro. In this study we have hypothesized that sperm retained acetylated histones and nGPx4 are implicated in paternal chromatin decondensation and male pronucleus formation at fertilization. Indeed, significant higher amounts of acetylated histone H4 and acetylated histone H3 were observed by both immunofluorescence and western blotting in nGPx4-KO sperm vs WT ones...
August 12, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28800532/cell-cycle-arrest-mediated-by-cd-induced-dna-damage-in-arabidopsis-root-tips
#6
Weina Cui, Hetong Wang, Jie Song, Xia Cao, Hilary J Rogers, Dennis Francis, Chunyun Jia, Lizong Sun, Meifang Hou, Yuesuo Yang, Peidong Tai, Wan Liu
Accumulating evidence demonstrates that the aberrant expression of cell cycle regulation and DNA repair genes can result in abnormal cell proliferation and genomic instability in eukaryotic cells under different stresses. Herein, Arabidopsis thaliana (Arabidopsis) seedlings were grown hydroponically on 0.5 × MS media containing cadmium (Cd) at 0-2.5mgL(-1) for 5d of treatment. Real time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis revealed that expression of DNA damage repair and cell cycle regulation genes, including BRCA1, MRE11, WEE1, CDKA;1 and PCNA1, showed an inverted U-shaped dose-response...
August 8, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28798233/the-atad2-bromodomain-binds-different-acetylation-marks-on-the-histone-h4-in-similar-fuzzy-complexes
#7
Cassiano Langini, Amedeo Caflisch, Andreas Vitalis
Bromodomains are protein modules adopting conserved helix-bundle folds. Some bromodomain-containing proteins, such as ATPase family AAA domain-containing protein 2 (ATAD2), isoform A, have attracted much interest because they are overexpressed in many types of cancer. Bromodomains bind to acetylated lysine residues on histone tails and thereby facilitate the reading of the histone code. Epigenetic regulators in general have been implicated as indicators, mediators, or causes of a large number of diseases and disorders...
August 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28790852/impact-of-combined-treatment-with-nimesulide-and-cisplatin-on-oral-carcinoma-cells
#8
Aleksandra Barac, Goran Mitulovic, Seth Hallström, Sonja Zehetmayer, Matthaeus Ch Grasl, Boban M Erovic
BACKGROUND: Despite significant advances in diagnosis and therapy, the rate of survival of patients with oral cancers still remains poor as an appropriate treatment has not been found yet, due to side effects of chemo/radiotherapy. AIM: This study aimed to identify molecular mechanisms of cell death of oral cancer cells caused by treatment with a nonselective Cox-2 inhibitor in combination with a low-dose chemotherapeutic drug. METHODS: Squamous cell carcinoma (SCC) cells SCC9 and SCC25 were subjected to mono- and combination therapy with nimesulide and cisplatin...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28790150/phosphorylation-of-histone-h2a-at-serine-95-a-plant-specific-mark-involved-in-flowering-time-regulation-and-h2a-z-deposition
#9
Yanhua Su, Shiliang Wang, Fei Zhang, Han Zheng, Yana Liu, Tongtong Huang, Yong Ding
Phosphorylation of histone H3 affects transcription, chromatin condensation, and chromosome segregation. However, the role of phosphorylation of histone H2A remains unclear. Here, we found that Arabidopsis thaliana MUT9P-LIKE-KINASE (MLK4) phosphorylates histone H2A on serine 95, a plant-specific modification in the histone core domain. Mutations in MLK4 caused late flowering under long-day conditions but no notable phenotype under short days. MLK4 interacts with CIRCADIAN CLOCK ASSOCIATED1 (CCA1), which allows MLK4 to bind to the GIGANTEA (GI) promoter...
August 8, 2017: Plant Cell
https://www.readbyqxmd.com/read/28776290/synthesis-characterization-and-evaluation-of-cd-l-proline-2-a-novel-histone-deacetylase-inhibitor-that-induces-epigenetic-modification-of-histone-deacetylase-isoforms-in-a549-cells
#10
Anusha Chidambaram, Arunachalam Sekar, Kavya S H, Ramesh Kumar Chidambaram, Kalaiarasi Arunachalam, Senthilkumar G P, Ravikumar Vilwanathan
Histone deacetylases (HDACs) play an important role in the epigenetic regulation of gene expression through their effects on the compact chromatin structure. In clinical studies, several classes of histone deacetylase inhibitors (HDACi) have demonstrated potent anticancer activities with metal complexes. Hence, we synthesized cadmium-proline complexes using both the D- and L-isomers of proline and evaluated their biological activities by observing the efficiency of their inhibition of HDAC activity, ability to reduce the expression of HDAC isoforms in A549 cells and effect on apoptosis...
August 3, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28762874/reactivation-of-hyperglycemia-induced-hypocretin-hcrt-gene-silencing-by-n-acetyl-d-mannosamine-in-the-orexin-neurons-derived-from-human-ips-cells
#11
Koji Hayakawa, Yasuharu Sakamoto, Osamu Kanie, Atsuko Ohtake, Shusaku Daikoku, Yukishige Ito, Kunio Shiota
Orexin neurons regulate critical brain activities for controlling sleep, eating, emotions, and metabolism, and impaired orexin neuron function results in several neurological disorders. Therefore, restoring normal orexin function and understanding the mechanisms of loss or impairment of orexin neurons represent important goals. As a step toward that end, we generated human orexin neurons from induced pluripotent stem cells (hiPSCs) by treatment with N-acetyl-d-mannosamine (ManNAc) and its derivatives. The generation of orexin neurons was associated with DNA hypomethylation, histone H3/H4 hyperacetylation, and hypo-O-GlcNAcylation on the HCRT gene locus, and, thereby, the treatment of inhibitors of SIRT1 and OGT were effective at inducing orexin neurons from hiPSCs...
August 1, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28760776/tie2-associates-with-caveolae-and-regulates-caveolin-1-to-promote-their-nuclear-translocation
#12
Mohammad B Hossain, Rehnuma Shifat, Jingyi Li, Xuemei Luo, Kenneth R Hess, Yisel Rivera-Molina, Francisco P Martinez, Hong Jiang, Frederick F Lang, Mien-Chie Hung, Juan Fueyo, Candelaria Gomez-Manzano
DNA repair pathways are aberrant in cancer, enabling tumor cells to survive standard therapies-chemotherapy and radiotherapy. Our group previously reported that, upon irradiation, the membrane-bound tyrosine kinase receptor TIE2 translocates into the nucleus and phosphorylates histone H4 at Tyr51, recruiting ABL1 to the DNA repair complexes that participate in the non-homologous end-joining pathway. However, no specific molecular mechanisms of TIE2 endocytosis have been reported. Here, we show that irradiation or ligand-induced TIE2 trafficking is dependent on caveolin-1, the main component of caveolae...
July 31, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28757400/epigenetic-regulation-of-ec-sod-expression-in-aging-lung-fibroblasts-role-of-histone-acetylation
#13
Jesse Roman, Jianxin Zhu, Jeffrey D Ritzenthaler, Igor N Zelko
Lung disorders characterized by fibroproliferation and excessive deposition of extracellular matrices occur in late adulthood, and their pathological manifestations become more prominent with aging. The exact mechanisms linking aging and fibroproliferative disorders are unknown, but increased oxidative stress resulting in the accumulation of damaged proteins, DNA, and lipids is considered a major factor. In the lung, and especially in the pulmonary fibroblasts, the extracellular superoxide dismutase (EC-SOD) is a major antioxidant enzyme that has been implicated in pulmonary fibrosing disorders, among others...
July 27, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28751935/chk1-promotes-dna-damage-response-bypass-following-oxidative-stress-in-a-model-of-hydrogen-peroxide-associated-ulcerative-colitis-through-jnk-inactivation-and-chromatin-binding
#14
Kathrin Reissig, Andrew Silver, Roland Hartig, Antje Schinlauer, Diana Walluscheck, Thomas Guenther, Sandra Siedentopf, Jochen Ross, Diep-Khanh Vo, Albert Roessner, Angela Poehlmann-Nitsche
Dysregulation of c-Jun N-terminal kinase (JNK) activation promoted DNA damage response bypass and tumorigenesis in our model of hydrogen peroxide-associated ulcerative colitis (UC) and in patients with quiescent UC (QUC), UC-related dysplasia, and UC-related carcinoma (UC-CRC), thereby adapting to oxidative stress. In the UC model, we have observed features of oncogenic transformation: increased proliferation, undetected DNA damage, and apoptosis resistance. Here, we show that Chk1 was downregulated but activated in the acute and quiescent chronic phases...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28749244/radiation-protection-and-mitigation-potential-of-phenylbutyrate-delivered-via-oral-administration
#15
Alexandra C Miller, Rafael Rivas, Robert McMahon, Karvelisse Miller, Leonard Tesoro, Vilmar Villa, Daminik Yanushkevich, Paul Lison
PURPOSE: Phenylbutyrate (PB), a histone deacetylase inhibitor (HDACi) has demonstrated radiation protection in both in vitro and in vivo models. Studies previously demonstrated that PB and other HDAC inhibitors could inhibit radiation lethality in vivo by subcutaneous (s.c) injection. The objective of this study was to test the ability of oral PB treatment to protect against or to mitigate acute gamma radiation-induced lethality in vivo. MATERIALS AND METHODS: Human osteoblasts cells were used to evaluate radiation survival when PB was delivered pre- or post-radiation...
July 27, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28720323/rapid-divergence-of-histones-in-hydrozoa-cnidaria-and-evolution-of-a-novel-histone-involved-in-dna-damage-response-in-hydra
#16
Puli Chandramouli Reddy, Suyog Ubhe, Neha Sirwani, Rasika Lohokare, Sanjeev Galande
Histones are fundamental components of chromatin in all eukaryotes. Hydra, an emerging model system belonging to the basal metazoan phylum Cnidaria, provides an ideal platform to understand the evolution of core histone components at the base of eumetazoan phyla. Hydra exhibits peculiar properties such as tremendous regenerative capacity, lack of organismal senescence and rarity of malignancy. In light of the role of histone modifications and histone variants in these processes it is important to understand the nature of histones themselves and their variants in hydra...
June 15, 2017: Zoology: Analysis of Complex Systems, ZACS
https://www.readbyqxmd.com/read/28717009/acetylation-on-histone-h3-lysine-9-mediates-a-switch-from-transcription-initiation-to-elongation
#17
Leah A Gates, Jiejun Shi, Aarti D Rohira, Qin Feng, Bokai Zhu, Mark T Bedford, Cari A Sagum, Sung Yun Jung, Jun Qin, Ming-Jer Tsai, Sophia Y Tsai, Wei Li, Charles E Foulds, Bert W O'Malley
The transition from transcription initiation to elongation is a key regulatory step in gene expression, which requires RNA polymerase II (Pol II) to escape promoter proximal pausing on chromatin. While elongation factors promote pause release leading to transcription elongation, the role of epigenetic modifications during this critical transition step is poorly understood. Two histone marks on histone H3, lysine 4 trimethylation (H3K4me3) and lysine 9 acetylation (H3K9ac), co-localize on active gene promoters and are associated with active transcription...
July 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28708136/differential-requirements-for-tousled-like-kinases-1-and-2-in-mammalian-development
#18
Sandra Segura-Bayona, Philip A Knobel, Helena González-Burón, Sameh A Youssef, Aida Peña-Blanco, Étienne Coyaud, Teresa López-Rovira, Katrin Rein, Lluís Palenzuela, Julien Colombelli, Stephen Forrow, Brian Raught, Anja Groth, Alain de Bruin, Travis H Stracker
The regulation of chromatin structure is critical for a wide range of essential cellular processes. The Tousled-like kinases, TLK1 and TLK2, regulate ASF1, a histone H3/H4 chaperone, and likely other substrates, and their activity has been implicated in transcription, DNA replication, DNA repair, RNA interference, cell cycle progression, viral latency, chromosome segregation and mitosis. However, little is known about the functions of TLK activity in vivo or the relative functions of the highly similar TLK1 and TLK2 in any cell type...
July 14, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28696214/epigenetic-regulation-by-agonist-specific-aryl-hydrocarbon-receptor-recruitment-of-metastasis-associated-protein-2-selectively-induces-stanniocalcin-2-expression
#19
Aditya D Joshi, Ekram Hossain, Cornelis J Elferink
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates a plethora of target genes. Historically, the AhR has been studied as a regulator of xenobiotic metabolizing enzyme genes, notably cytochrome P4501A1 encoded by CYP1A1, in response to the exogenous prototypical ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). AhR activity depends on its binding to the xenobiotic response element (XRE) in partnership with the AhR nuclear translocator (Arnt). Recent studies identified stanniocalcin 2 (Stc2) as a novel AhR target gene responsive to the endogenous AhR agonist cinnabarinic acid (CA)...
September 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28695517/high-throughput-colorimetric-assay-for-identifying-parp-1-inhibitors-using-a-large-small-molecule-collection
#20
Elena Kotova, Alexei V Tulin
Poly(ADP-ribose)polymerase 1 (PARP-1) protein became a popular target for treatment of several types of cancer. A number of PARP-1 inhibitors are currently in clinical trials. Most of them were designed competitors with NAD for a binding site on PARP-1 molecule. This strategy resulted in a discovery of mainly nucleotide-like PARP-1 inhibitors, which may target not only PARP-1 but also other pathways involving NAD and other nucleotides. Many cancer types demonstrate rapid development of resistance to NAD-like PARP-1 inhibitors...
2017: Methods in Molecular Biology
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