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histone H3.2

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https://www.readbyqxmd.com/read/28237615/inhibition-of-dna-methylation-in-the-col1a2-promoter-by-anacardic-acid-prevents-uv-induced-decrease-of-type-i-procollagen-expression
#1
Min-Kyoung Kim, Eun Ju Kim, Yao Cheng, Mi Hee Shin, Jang-Hee Oh, Dong Hun Lee, Jin Ho Chung
Ultraviolet (UV) radiation decreases type I procollagen production mainly by inhibiting the TGF-β/Smad signaling pathway. Because further epigenetic regulatory mechanisms are unclear, we investigated the roles of DNA methylation and histone acetylation in UV-induced regulation of collagen type I alpha 2 (COL1A2) transcription in human dermal fibroblasts(HDFs). Anacardic acid (AA), a p300 histone acetyltransferase inhibitor, rescued the UV-induced decrease of type I procollagen expression in HDFs. Although UV irradiation induced global histone acetylation, it reduced the local recruitment of histone H3 acetylation as well as p300, and Smad2/3 to the p300 binding site (-1406/-1393) in the COL1A2 promoter as shown by chromatin immunoprecipitation...
February 22, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28235947/human-centromeric-cenp-a-chromatin-is-a-homotypic-octameric-nucleosome-at-all-cell-cycle-points
#2
Yael Nechemia-Arbely, Daniele Fachinetti, Karen H Miga, Nikolina Sekulic, Gautam V Soni, Dong Hyun Kim, Adeline K Wong, Ah Young Lee, Kristen Nguyen, Cees Dekker, Bing Ren, Ben E Black, Don W Cleveland
Chromatin assembled with centromere protein A (CENP-A) is the epigenetic mark of centromere identity. Using new reference models, we now identify sites of CENP-A and histone H3.1 binding within the megabase, α-satellite repeat-containing centromeres of 23 human chromosomes. The overwhelming majority (97%) of α-satellite DNA is found to be assembled with histone H3.1-containing nucleosomes with wrapped DNA termini. In both G1 and G2 cell cycle phases, the 2-4% of α-satellite assembled with CENP-A protects DNA lengths centered on 133 bp, consistent with octameric nucleosomes with DNA unwrapping at entry and exit...
February 24, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28230279/folate-protects-hepatocytes-of-hyperhomocysteinemia-mice-from-apoptosis-via-cystic-fibrosis-transmembrane-conductance-regulator-cftr-activated-endoplasmic-reticulum-stress
#3
Anning Yang, Yue Sun, Caiyan Mao, Songhao Yang, Min Huang, Mei Deng, Ning Ding, Xiaoling Yang, Minghao Zhang, Shaoju Jin, Yideng Jiang, Ying Huang
Folate deficiency is a known risk factor for liver injury; however, the underlying mechanism remains unclear. In this study, we employed a high homocysteine-induced liver injury model of Apolipoprotein E-deficient (ApoE(-/-) ) mice fed high-methionine diet and found that high homocysteine induced endoplasmic reticulum (ER) stress and liver cell apoptosis by downregulation of cystic fibrosis transmembrane conductance regulator (CFTR) expression; observations that were attenuated with supplementation of dietary folate...
February 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28229514/mutations-in-genes-encoding-polycomb-repressive-complex-2-subunits-cause-weaver-syndrome
#4
Eri Imagawa, Ken Higashimoto, Yasunari Sakai, Chikahiko Numakura, Nobuhiko Okamoto, Satoko Matsunaga, Akihide Ryo, Yoshinori Sato, Masafumi Sanefuji, Kenji Ihara, Yui Takada, Gen Nishimura, Hirotomo Saitsu, Takeshi Mizuguchi, Satoko Miyatake, Mitsuko Nakashima, Noriko Miyake, Hidenobu Soejima, Naomichi Matsumoto
Weaver syndrome is a rare congenital overgrowth disorder caused by heterozygous mutations in EZH2 (enhancer of zeste homolog 2) or EED (embryonic ectoderm development). EZH2 and EED are core components of the polycomb repressive complex 2 (PRC2), which possesses histone methyltransferase activity and catalyzes trimethylation of histone H3 at lysine 27. Here, we analyzed eight probands with clinically suspected Weaver syndrome by whole exome sequencing and identified three mutations: a 25.4-kb deletion partially involving EZH2 and CUL1 (individual 1), a missense mutation (c...
February 22, 2017: Human Mutation
https://www.readbyqxmd.com/read/28228845/histone-and-dna-methylation-control-by-h3-serine-10-threonine-11-phosphorylation-in-the-mouse-zygote
#5
Jie Lan, Konstantin Lepikhov, Pascal Giehr, Joern Walter
BACKGROUND: In the mammalian zygote, epigenetic reprogramming is a tightly controlled process of coordinated alterations of histone and DNA modifications. The parental genomes of the zygote show distinct patterns of histone H3 variants and distinct patterns of DNA and histone modifications. The molecular mechanisms linking histone variant-specific modifications and DNA methylation reprogramming during the first cell cycle remain to be clarified. RESULTS: Here, we show that the degree and distribution of H3K9me2 and of DNA modifications (5mC/5hmC) are influenced by the phosphorylation status of H3S10 and H3T11...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28224725/quisinostat-treatment-improves-histone-acetylation-and-developmental-competence-of-porcine-somatic-cell-nuclear-transfer-embryos
#6
Long Jin, Qing Guo, Hai-Ying Zhu, Xiao-Xu Xing, Guang-Lei Zhang, Mei-Fu Xuan, Qi-Rong Luo, Zhao-Bo Luo, Jun-Xia Wang, Xi-Jun Yin, Jin-Dan Kang
Abnormal epigenetic modifications are considered a main contributing factor to low cloning efficiency. In the present study, we explored the effects of quisinostat, a novel histone deacetylase inhibitor, on blastocyst formation rate in porcine somatic-cell nuclear transfer (SCNT) embryos, on acetylation of histone H3 lysine 9 (AcH3K9), and on expression of POU5F1 protein and apoptosis-related genes BAX and BCL2. Our results showed that treatment with 10 nM quisinostat for 24 h significantly improved the development of reconstructed embryos compared to the untreated group (19...
February 22, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/28223321/a-non-canonical-function-of-ezh2-preserves-immune-homeostasis
#7
Ajithkumar Vasanthakumar, Dakang Xu, Aaron Tl Lun, Andrew J Kueh, Klaas Pjm van Gisbergen, Nadia Iannarella, Xiaofang Li, Liang Yu, Die Wang, Bryan Rg Williams, Stanley Cw Lee, Ian J Majewski, Dale I Godfrey, Gordon K Smyth, Warren S Alexander, Marco J Herold, Axel Kallies, Stephen L Nutt, Rhys S Allan
Enhancer of zeste 2 (Ezh2) mainly methylates lysine 27 of histone-H3 (H3K27me3) as part of the polycomb repressive complex 2 (PRC2) together with Suz12 and Eed. However, Ezh2 can also modify non-histone substrates, although it is unclear whether this mechanism has a role during development. Here, we present evidence for a chromatin-independent role of Ezh2 during T-cell development and immune homeostasis. T-cell-specific depletion of Ezh2 induces a pronounced expansion of natural killer T (NKT) cells, although Ezh2-deficient T cells maintain normal levels of H3K27me3...
February 21, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28214660/enhancer-of-zeste-homologue-2-plays-an-important-role-in-neuroblastoma-cell-survival-independent-of-its-histone-methyltransferase-activity
#8
Laurel T Bate-Eya, Hinco J Gierman, Marli E Ebus, Jan Koster, Huib N Caron, Rogier Versteeg, M Emmy M Dolman, Jan J Molenaar
Neuroblastoma is predominantly characterised by chromosomal rearrangements. Next to V-Myc Avian Myelocytomatosis Viral Oncogene Neuroblastoma Derived Homolog (MYCN) amplification, chromosome 7 and 17q gains are frequently observed. We identified a neuroblastoma patient with a regional 7q36 gain, encompassing the enhancer of zeste homologue 2 (EZH2) gene. EZH2 is the histone methyltransferase of lysine 27 of histone H3 (H3K27me3) that forms the catalytic subunit of the polycomb repressive complex 2. H3K27me3 is commonly associated with the silencing of genes involved in cellular processes such as cell cycle regulation, cellular differentiation and cancer...
February 16, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28209712/mycobacterium-tuberculosis-esxl-inhibit-mhc-ii-expression-by-promoting-hypermethylation-in-class-ii-transactivator-loci-in-macrophages
#9
Srabasti Sengupta, Saba Naz, Ishani Das, Abdul Ahad, Avinash Padhi, Sumanta Naik, Geetanjali Ganguli, Kaliprasad Patnaik, Sunil Kumar Raghav, Vinay Nandicoori, Avinash Sonawane
Mycobacterium tuberculosis (Mtb) is known to modulate the host immune responses to facilitate its persistence inside the host cells. One of the key mechanisms includes repression of class-II transactivator (CIITA) and MHC-II expression in infected macrophages. However, the precise mechanism of CIITA and MHC-II down-regulation is not well studied. Mtb 6-kDa early secretory antigenic target (ESAT-6) is a known potent virulence and antigenic determinant. Mtb genome encodes 23 such ESAT-6 family proteins. We herein report that Mtb and M...
February 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28186757/thieno-3-2-b-pyrrole-5-carboxamides-as-new-reversible-inhibitors-of-histone-lysine-demethylase-kdm1a-lsd1-part-2-structure-based-drug-design-and-structure-activity-relationship
#10
Paola Vianello, Luca Sartori, Federica Amigoni, Anna Cappa, Giovanni Fagá, Raimondo Fattori, Elena Legnaghi, Giuseppe Ciossani, Andrea Mattevi, Giuseppe Meroni, Loris Moretti, Valentina Cecatiello, Sebastiano Pasqualato, Alessia Romussi, Florian Thaler, Paolo Trifiró, Oronza A Botrugno, Manuela Villa, Paola Dessanti, Saverio Minucci, Stefania Vultaggio, Elisa Zagarrí, Mario Varasi, Ciro Mercurio
The balance of methylation levels at histone H3 lysine 4 (H3K4) is regulated by KDM1A (LSD1). KDM1A is overexpressed in several tumor types, thus representing an emerging target for the development of novel cancer therapeutics. We have previously described (Part 1) the identification of thieno[3,2-b]pyrrole-5-carboxamides, as novel reversible inhibitors of KDM1A, whose preliminary exploration resulted in compound 2 with biochemical IC50 = 160 nM. We now report the structure-guided optimization of this chemical series, based on multiple ligand/KDM1A-CoRest co-crystal structures, which led to several extremely potent inhibitors...
February 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28183840/imaging-characteristics-of-pediatric-diffuse-midline-gliomas-with-histone-h3-k27m-mutation
#11
M S Aboian, D A Solomon, E Felton, M C Mabray, J E Villanueva-Meyer, S Mueller, S Cha
BACKGROUND AND PURPOSE: The 2016 World Health Organization Classification of Tumors of the Central Nervous System includes "diffuse midline glioma with histone H3 K27M mutation" as a new diagnostic entity. We describe the MR imaging characteristics of this new tumor entity in pediatric patients. MATERIALS AND METHODS: We retrospectively reviewed imaging features of pediatric patients with midline gliomas with or without the histone H3 K27 mutation. We evaluated the imaging features of these tumors on the basis of location, enhancement pattern, and necrosis...
February 9, 2017: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/28177835/analysis-of-the-histone-cluster-in-senegalese-sole-solea-senegalensis-evidence-for-a-divergent-evolution-of-two-canonical-histone-clusters
#12
Manuel Alejandro Merlo, Roger Iziga, Silvia Portela, Ismael Cross, Nadezda Kosyakova, Thomas Liehr, Manuel Manchado, Laureana Rebordinos
The Senegalese sole (Solea senegalensis) is commercially very important, and is a priority species for aquaculture product diversification. The main histone cluster was found in two BAC clones. However, two replacement histones (H1.0 and H3.3) were found in another BAC clone. Different types of canonical H2A and H2B have been found in one species for the first time. Phylogenetic analysis demonstrated that the different H1, H2A and H2B types were all more similar to each other than to canonical histones from other species...
December 10, 2016: Genome Génome / Conseil National de Recherches Canada
https://www.readbyqxmd.com/read/28174273/h3k4me3-induces-allosteric-conformational-changes-in-the-dna-binding-and-catalytic-regions-of-the-v-d-j-recombinase
#13
John Bettridge, Chan Hyun Na, Akhilesh Pandey, Stephen Desiderio
V(D)J recombination is initiated by the recombination-activating gene (RAG) recombinase, consisting of RAG-1 and RAG-2 subunits. The susceptibility of gene segments to cleavage by RAG is associated with histone modifications characteristic of active chromatin, including trimethylation of histone H3 at lysine 4 (H3K4me3). Binding of H3K4me3 by a plant homeodomain (PHD) in RAG-2 stimulates substrate binding and catalysis, which are functions of RAG-1. This has suggested an allosteric mechanism in which information regarding occupancy of the RAG-2 PHD is transmitted to RAG-1...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28171866/selective-biological-responses-of-phagocytes-and-lungs-to-purified-histones
#14
Fatemeh Fattahi, Jamison J Grailer, Hope Lu, Rachel S Dick, Michella Parlett, Firas S Zetoune, Gabriel Nuñez, Peter A Ward
Histones invoke strong proinflammatory responses in many different organs and cells. We assessed biological responses to purified or recombinant histones, using human and murine phagocytes and mouse lungs. H1 had the strongest ability in vitro to induce cell swelling independent of requirements for toll-like receptors (TLRs) 2 or 4. These responses were also associated with lactate dehydrogenase release. H3 and H2B were the strongest inducers of [Ca2+]i elevations in phagocytes. Cytokine and chemokine release from mouse and human phagocytes was predominately a function of H2A and H2B...
February 8, 2017: Journal of Innate Immunity
https://www.readbyqxmd.com/read/28171799/synergistic-antitumor-effect-of-histone-deacetylase-inhibitor-and-doxorubicin-in-peripheral-t-cell-lymphoma
#15
Huilai Zhang, Ling Dong, Qingqing Chen, Lingzhe Kong, Bin Meng, Huaqing Wang, Kai Fu, Xi Wang, Qiang Pan-Hammarström, Ping Wang, Xianhuo Wang
Chidamide (CS055) is a new and highly selective histone deacetylase inhibitor displaying significant single-agent activity in peripheral T-cell lymphoma (PTCL). But there is little known the synergistic effect between CS055 and chemotherapy. The purpose of this study is to explore the synergistic effect and molecular mechanisms of CS055 combination with Doxorubicin in PTCL cells. We found that CS055 showed dose- and time-dependent inhibition effects on PTCL cell. Meanwhile, the synergistic effect was significantly observed after combination treatment with lower drug-concentration of CS055 and Doxorubicin...
January 25, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28165227/discovery-of-peptidomimetic-ligands-of-eed-as-allosteric-inhibitors-of-prc2
#16
Kimberly D Barnash, Juliana The, Jacqueline L Norris-Drouin, Stephanie H Cholensky, Beau M Worley, Fengling Li, Jacob I Stuckey, Peter J Brown, Masoud Vedadi, Cheryl H Arrowsmith, Stephen V Frye, Lindsey I James
The function of EED within polycomb repressive complex 2 (PRC2) is mediated by a complex network of protein-protein interactions. Allosteric activation of PRC2 by binding of methylated proteins to the embryonic ectoderm development (EED) aromatic cage is essential for full catalytic activity, but details of this regulation are not fully understood. EED's recognition of the product of PRC2 activity, histone H3 lysine 27 trimethylation (H3K27me3), stimulates PRC2 methyltransferase activity at adjacent nucleosomes leading to H3K27me3 propagation and, ultimately, gene repression...
February 22, 2017: ACS Combinatorial Science
https://www.readbyqxmd.com/read/28161762/validation-of-an-enzyme-linked-immunosorbent-assay-for-the-quantification-of-citrullinated-histone-h3-as-a-marker-for-neutrophil-extracellular-traps-in-human-plasma
#17
Charlotte Thålin, Maud Daleskog, Sophie Paues Göransson, Daphne Schatzberg, Julie Lasselin, Ann-Charlotte Laska, Anders Kallner, Thomas Helleday, Håkan Wallén, Mélanie Demers
There is an emerging interest in the diverse functions of neutrophil extracellular traps (NETs) in a variety of disease settings. However, data on circulating NETs rely largely upon surrogate NET markers such as cell-free DNA, nucleosomes, and NET-associated enzymes. Citrullination of histone H3 by peptidyl arginine deiminase 4 (PAD4) is central for NET formation, and citrullinated histone H3 (H3Cit) is considered a NET-specific biomarker. We therefore aimed to optimize and validate a new enzyme-linked immunosorbent assay (ELISA) to quantify the levels of H3Cit in human plasma...
February 4, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28155248/mutants-in-the-imprinted-pickle-related-2-gene-suppress-seed-abortion-of-fertilization-independent-seed-class-mutants-and-paternal-excess-interploidy-crosses-in-arabidopsis
#18
Fang Huang, Qian-Hao Zhu, Anyu Zhu, Xiaoba Wu, Liqiong Xie, Xianjun Wu, Chris Helliwell, Abed Chaudhury, E Jean Finnegan, Ming Luo
Endosperm cellularization is essential for embryo development and viable seed formation. Loss of function of the FERTILIZATION INDEPENDENT SEED (FIS) class Polycomb genes, which mediate histone H3 lysine27 trimethylation (H3K27me3), as well as imbalanced contributions of parental genomes interrupt this process. What causes the failure of cellularization is poorly understood. In this study, we identified PICKLE RELATED 2 (PKR2), mutations which suppress seed abortion in fis1/mea by restoring endosperm cellularization...
February 3, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28139057/synthesis-of-ubiquitylated-histone-h3-using-a-thiirane-linker-for-chemical-ligation
#19
Toru Kawakami, Yuichi Mishima, Hironobu Hojo, Isao Suetake
Post-translational modifications of histone proteins, which form nucleosome cores, play an important role in gene regulation. Ubiquitin modification is one such modification. We previously reported on the use of a thiirane linker to introduce a 1,2-aminothiol moiety at a cysteine residue for native chemical ligation with peptide thioesters, which permitted isopeptide mimetics to be produced. In this report, we describe the preparation of the ubiquitylated full length histone H3 at the 18 position and the construction of tetranucleosomes with recombinant histones H2A, H2B, H4, and DNA, which are slightly more stable than those that are prepared without ubiquitin modification...
January 31, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28138058/basic-pentacysteine-proteins-repress-abscisic-acid-insensitive4-expression-via-direct-recruitment-of-the-polycomb-repressive-complex-2-in-arabidopsis-root-development
#20
Ying Mu, Meijuan Zou, Xuwu Sun, Baoye He, Xiumei Xu, Yini Liu, Lixin Zhang, Wei Chi
Plant transcription factors generally act in complex regulatory networks that function at multiple levels to govern plant developmental programs. Dissection of the interconnections among different classes of transcription factors can elucidate these regulatory networks and thus improve our understanding of plant development. Here, we investigated the molecular and functional relationships of the transcription factors ABSCISIC ACID INSENSITIVE 4 (ABI4) and members of the BASIC PENTACYSTEINE (BPC) family in lateral root (LR) development of Arabidopsis thaliana Genetic analysis showed that BPCs promote LR development by repressing ABI4 expression...
January 30, 2017: Plant & Cell Physiology
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