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https://www.readbyqxmd.com/read/28723643/methyltransferase-g9a-promotes-cervical-cancer-angiogenesis-and-decreases-patient-survival
#1
Ruey-Jien Chen, Chia-Tung Shun, Men-Luh Yen, Chia-Hung Chou, Ming-Chieh Lin
Research suggests that the epigenetic regulator G9a, a H3K9 histone methyltransferase, is involved in cancer invasion and metastasis. Here we show that G9a is linked to cancer angiogenesis and poor patient survival. Invasive cervical cancer has a higher G9a expression than cancer precursors or normal epithelium. Pharmacological inhibition and genetic silencing of G9a suppresses H3K9 methylation, cancer cell proliferation, angiogenesis, and cancer cell invasion/migration, but not apoptosis. Microarray and quantitative reverse transcription polymerase chain reaction analyses reveal that G9a induces a cohort of angiogenic factors that include angiogenin, interleukin-8, and C-X-C motif chemokine ligand 16...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723639/integrated-analysis-of-the-molecular-action-of-vorinostat-identifies-epi-sensitised-targets-for-combination-therapy
#2
Jodie F Hay, Katrina Lappin, Fabio Liberante, Laura M Kettyle, Kyle B Matchett, Alexander Thompson, Ken I Mills
Several histone deacetylase inhibitors including Vorinostat have received FDA approval for the treatment of haematological malignancies. However, data from these trials indicate that Vorinostat has limited efficacy as a monotherapy, prompting the need for rational design of combination therapies. A number of epi-sensitised pathways, including sonic hedgehog (SHH), were identified in AML cells by integration of global patterns of histone H3 lysine 9 (H3K9) acetylation with transcriptomic analysis following Vorinostat-treatment...
July 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28718376/riz1-and-histone-methylation-status-in-pituitary-adenomas
#3
Yake Xue, Ruokun Chen, Wei Du, Fengdong Yang, Xinting Wei
RIZ1 displays strong tumor-suppressive activities, which has a potential histone methyltransferase activity. The objective of the study was to evaluate the level and the methylation status of RIZ1 and analyze its association with clinicopathological features and the histone in the pituitary adenomas. We found that RIZ1-positive cases were 11/50 and H-Scores 22.75 ± 11.83 in invasive pituitary adenomas and 26/53 and 66.3 ± 21.7 in non-invasive pituitary adenomas (χ(2) = 8.182, p = 0.004). RIZ1 and C-myc showed the opposite trend in these cases...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28716006/ethylene-induces-combinatorial-effects-of-histone-h3-acetylation-in-gene-expression-in-arabidopsis
#4
Likai Wang, Fan Zhang, Siddharth Rode, Kevin K Chin, Eun Esther Ko, Jonghwan Kim, Vishwanath R Iyer, Hong Qiao
BACKGROUND: Histone acetylation and deacetylation are essential for gene regulation and have been implicated in the regulation of plant hormone responses. Many studies have indicated the role of histone acetylation in ethylene signaling; however, few studies have investigated how ethylene signaling regulates the genomic landscape of chromatin states. Recently, we found that ethylene can specifically elevate histone H3K14 acetylation and the non-canonical histone H3K23 acetylation in etiolated seedlings and the gene activation is positively associated with the elevation of H3K14Ac and H3K23Ac in response to ethylene...
July 17, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28715960/histone-methylation-by-set-domain-proteins-in-fungi
#5
Michael Freitag
Histone-modifying enzymes are responsible for regulating transcription, recombination, DNA repair, DNA replication, chromatid cohesion, and chromosome segregation. Fungi are ideally suited for comparative chromatin biology because sequencing of numerous genomes from many clades is coupled to existing rich methodology that allows truly holistic approaches, integrating evolutionary biology with mechanistic molecular biology and ecology, promising applications in medicine or plant pathology. While genome information is rich, mechanistic studies on histone modifications are largely restricted to two yeasts, Saccharomyces cerevisiae and Schizosaccharomyces pombe, and one filamentous fungus, Neurospora crassa-three species that arguably are not representative of this diverse kingdom...
July 17, 2017: Annual Review of Microbiology
https://www.readbyqxmd.com/read/28710961/epigenetic-modification-differences-between-fetal-fibroblast-cells-and-mesenchymal-stem-cells-of-the-arbas-cashmere-goat
#6
Xiao Wang, Zhimin Wang, Qing Wang, Hefei Wang, Hao Liang, Dongjun Liu
To explore the epigenetic mechanisms regulating mesenchymal stem cells, we analyzed epigenetic patterns in control goat fetal fibroblast cells (gFFCs), adipose-derived stem cells (gADSCs), bone marrow stromal cells (gBMSCs), and muscle-derived satellite cells (gMDSCs). We found that the 5mC content of gBMSC genomes was lower than that of gFFC genomes, while the 5mC content of gADSC and gMDSC genomes surpassed that of gFFC genomes. H3K9 acetylation did not differ significantly among those cells; gFFCs, gADSCs, and gMDSCs contained acetylated H3K9, H3K14, H3K18, H4K5, and H4K12, but gBMSCs contained almost no acetylated H4K5 and H4K12...
July 9, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28706533/inhibition-of-histone-h3k9-methylation-by-bix-01294-promotes-stress-induced-microspore-totipotency-and-enhances-embryogenesis-initiation
#7
Eduardo Berenguer, Ivett Bárány, María-Teresa Solís, Yolanda Pérez-Pérez, María C Risueño, Pilar S Testillano
Microspore embryogenesis is a process of cell reprogramming, totipotency acquisition and embryogenesis initiation, induced in vitro by stress treatments and widely used in plant breeding for rapid production of doubled-haploids, but its regulating mechanisms are still largely unknown. Increasing evidence has revealed epigenetic reprogramming during microspore embryogenesis, through DNA methylation, but less is known about the involvement of histone modifications. In this study, we have analyzed the dynamics and possible role of histone H3K9 methylation, a major repressive modification, as well as the effects on microspore embryogenesis initiation of BIX-01294, an inhibitor of histone methylation, tested for the first time in plants, in Brassica napus and Hordeum vulgare...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28701802/osthole-improves-function-of-periodontitis-periodontal-ligament-stem-cells-via-epigenetic-modification-in-cell-sheets-engineering
#8
Jin Sun, Zhiwei Dong, Yang Zhang, Xiaoning He, Dongdong Fei, Fang Jin, Lin Yuan, Bei Li, Yan Jin
Inflammatory microenvironment causes the change of epigenetic modification in periodontal ligament stem cells derived from periodontitis tissues (P-PDLSCs), which results in defective osteogenic differentiation compared to cells from healthy tissues. It's urgent to explore therapeutic strategies aimed at epigenetic targets associated with the regenerative ability of PDLSCs. Osthole, a small-molecule compound extracted from Chinese herbs, has been documented to promote osteogenesis and cell sheets formation of healthy PDLSCs...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28692045/impact-of-histone-demethylase-kdm3a-dependent-ap-1-transactivity-on-hepatotumorigenesis-induced-by-pi3k-activation
#9
T Nakatsuka, K Tateishi, Y Kudo, K Yamamoto, H Nakagawa, H Fujiwara, R Takahashi, K Miyabayashi, Y Asaoka, Y Tanaka, H Ijichi, Y Hirata, M Otsuka, M Kato, J Sakai, M Tachibana, H Aburatani, Y Shinkai, K Koike
Epigenetic gene regulation linked to oncogenic pathways is an important focus of cancer research. KDM3A, a histone H3 lysine 9 (H3K9) demethylase, is known to have a pro-tumorigenic function. Here, we showed that KDM3A contributes to liver tumor formation through the phosphatidylinositol 3-kinase (PI3K) pathway, which is often activated in hepatocellular carcinoma. Loss of Kdm3a attenuated tumor formation in Pik3ca transgenic (Tg) mouse livers. Transcriptome analysis of pre-cancerous liver tissues revealed that the expression of activator protein 1 (AP-1) target genes was induced by PI3K activation, but blunted upon Kdm3a ablation...
July 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28682306/unique-roles-for-histone-h3k9me-states-in-rnai-and-heritable-silencing-of-transcription
#10
Gloria Jih, Nahid Iglesias, Mark A Currie, Natarajan V Bhanu, Joao A Paulo, Steven P Gygi, Benjamin A Garcia, Danesh Moazed
Heterochromatic DNA domains play important roles in regulation of gene expression and maintenance of genome stability by silencing repetitive DNA elements and transposons. From fission yeast to mammals, heterochromatin assembly at DNA repeats involves the activity of small noncoding RNAs (sRNAs) associated with the RNA interference (RNAi) pathway(1-9). Typically, sRNAs, originating from long noncoding RNAs, guide Argonaute-containing effector complexes to complementary nascent RNAs to initiate histone H3 lysine 9 di- and tri-methylation (H3K9me2 and H3K9me3, respectively) and heterochromatin formation(10-17)...
June 22, 2017: Nature
https://www.readbyqxmd.com/read/28677817/inhibition-of-the-hdac-suv39-g9a-pathway-restores-the-expression-of-dna-damage-dependent-major-histocompatibility-complex-class%C3%A2-i-related-chain%C3%A2-a%C3%A2-and%C3%A2-b-in-cancer-cells
#11
Nakako Izumi Nakajima, Atsuko Niimi, Mayu Isono, Takahiro Oike, Hiro Sato, Takashi Nakano, Atsushi Shibata
Immunotherapy is expected to be promising as a next generation cancer therapy. Immunoreceptors are often activated constitutively in cancer cells, however, such levels of ligand expression are not effectively recognized by the native immune system due to tumor microenvironmental adaptation. Studies have demonstrated that natural-killer group 2, member D (NKG2D), a major activating immunoreceptor, responds to DNA damage. The upregulation of major histocompatibility complex class I-related chain A and B (MICA/B) (members of NKG2D ligands) expression after DNA damage is associated with NK cell-mediated killing of cancer cells...
June 30, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28655069/delivery-of-parasite-cdg7_flc_0990-rna-transcript-into-intestinal-epithelial-cells-during-cryptosporidium-parvum-infection-suppresses-host-cell-gene-transcription-through-epigenetic-mechanisms
#12
Yang Wang, Ai-Yu Gong, Shibin Ma, Xiqiang Chen, Juliane K Strauss-Soukup, Xian-Ming Chen
Cryptosporidial infection causes dysregulated transcription of host genes key to intestinal epithelial homeostasis, but the underlying mechanisms remain obscure. Previous studies demonstrate that several C. parvum RNA transcripts are selectively delivered into epithelial cells during host cell invasion and may modulate gene transcription in infected cells. We report here that C. parvum infection suppresses the transcription of LRP5, SLC7A8, and IL33 genes in infected intestinal epithelium. Trans-suppression of these genes in infected host cells is associated with promoter enrichment of suppressive epigenetic markers (i...
June 27, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28654693/fatty-acid-synthase-reprograms-the-epigenome-in-uterine-leiomyosarcomas
#13
Min Guan, Xiwei Wu, Peiguo Chu, Warren A Chow
SK-UT-1 uterine leiomyosarcomas (Ut-LMS) cells were transduced with a fatty acid synthase (FASN)-containing retroviral vector to recapitulate the "lipogenic phenotype of cancer." Consistent with this model, forced expression of FASN enhanced SK-UT-1 proliferation, migration, and cellular motion. Further investigation showed FASN promotes trimethylation of H3K9 (H3K9me3) and acetylation of H3K27 (H3K27ac) in SK-UT-1 cells. In contrast, siRNA targeting of FASN in high endogenous FASN expressing SK-LMS-1 Ut-LMS cells inhibits trimethylation of H3K9 and acetylation of H3K27...
2017: PloS One
https://www.readbyqxmd.com/read/28653878/sirtuin-6-plays-an-oncogenic-role-and-induces-cell-autophagy-in-esophageal-cancer-cells
#14
Nan Huang, Zhiwei Liu, Jiabei Zhu, Zhongqi Cui, Yuguang Li, Yongchun Yu, Fenyong Sun, Qiuhui Pan, Qingyuan Yang
Sirtuin 6, a member of sirtuin family, is generally regarded as a tumor suppressor as it participates in suppressing hypoxia-inducible factor 1α and MYC transcription activity by deacetylating H3K9 (histone H3 lysine 9) and H3K56 (histone H3 lysine) at promoters of target genes, leading to the aerobic glycolysis inhibition and cell growth suppression. However, its expression has recently been reported to be highly elevated in a series of tumors, including prostate cancer, breast cancer, and non-small cell lung cancer, indicating that sirtuin 6 plays dual roles in tumorigenicity in a cell/tumor type-specific manner...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28650521/jmj27-an-arabidopsis-h3k9-histone%C3%A2-demethylase-modulates-defense-against-pseudomonas-syringae%C3%A2-and%C3%A2-flowering%C3%A2-time
#15
Aditya Dutta, Pratibha Choudhary, Julie Caruana, Ramesh Raina
Histone methylation is known to dynamically regulate diverse developmental and physiological processes. Histone methyl marks are written by methyltransferases and erased by demethylases, and result in modification of chromatin structure to repress or activate transcription. However, little is known about how histone methylation may regulate defense mechanisms and flowering time in plants. Here we report characterization of JmjC DOMAIN-CONTAINING PROTEIN 27 (JMJ27), an Arabidopsis JHDM2 (JmjC domain-containing histone demethylase 2) family protein, which modulates defense against pathogens and flowering time...
June 26, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28644986/designing-novel-inhibitors-against-histone-acetyltransferase-hat-%C3%A2-gcn5-of-plasmodium-falciparum
#16
Amarjeet Kumar, Krishanu Bhowmick, Kunwar Somesh Vikramdeo, Neelima Mondal, Naidu Subbarao, Suman Kumar Dhar
During active proliferation phase of intra-erythrocytic cycle, the genome of P. falciparum is regulated epigenetically and evolutionary conserved parasite-specific histone proteins are extensively acetylated. The reversible process of lysine acetylation, causing transcriptional activation and its deacetylation, causing transcriptional repression is regulated by balanced activities of HATs and HDACs. They are also known to regulate antigenic variations and gametocytic conversion in P. falciparum. These histone modifying enzymes have been identified as potential targets for development of anitmalarials in literature...
June 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28636937/the-conserved-rna-binding-cyclophilin-rct1-regulates-small-rna-biogenesis-and-splicing-independent-of-heterochromatin-assembly
#17
An-Yun Chang, Stephane E Castel, Evan Ernst, Hyun Soo Kim, Robert A Martienssen
RNAi factors and their catalytic activities are essential for heterochromatin assembly in S. pombe. This has led to the idea that siRNAs can promote H3K9 methylation by recruiting the cryptic loci regulator complex (CLRC), also known as recombination in K complex (RIKC), to the nucleation site. The conserved RNA-binding protein Rct1 (AtCyp59/SIG-7) interacts with splicing factors and RNA polymerase II. Here we show that Rct1 promotes processing of pericentromeric transcripts into siRNAs via the RNA recognition motif...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28635654/the-identification-of-a-sirt6-activator-from-brown-algae-fucus-distichus
#18
Minna K Rahnasto-Rilla, Padraig McLoughlin, Tomasz Kulikowicz, Maire Doyle, Vilhelm A Bohr, Maija Lahtela-Kakkonen, Luigi Ferrucci, Maria Hayes, Ruin Moaddel
Brown seaweeds contain many bioactive compounds, including polyphenols, polysaccharides, fucosterol, and fucoxantin. These compounds have several biological activities, including anti-inflammatory, hepatoprotective, anti-tumor, anti-hypertensive, and anti-diabetic activity, although in most cases their mechanisms of action are not understood. In this study, extracts generated from five brown algae (Fucus dichitus, Fucus vesiculosus (Linnaeus), Cytoseira tamariscofolia, Cytoseira nodacaulis, Alaria esculenta) were tested for their ability to activate SIRT6 resulting in H3K9 deacetylation...
June 21, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28630300/g9a-drives-hypoxia-mediated-gene-repression-for-breast-cancer-cell-survival-and-tumorigenesis
#19
Francesco Casciello, Fares Al-Ejeh, Greg Kelly, Donal J Brennan, Shin Foong Ngiow, Arabella Young, Thomas Stoll, Karolina Windloch, Michelle M Hill, Mark J Smyth, Frank Gannon, Jason S Lee
G9a is an epigenetic regulator that methylates H3K9, generally causing repression of gene expression, and participates in diverse cellular functions. G9a is genetically deregulated in a variety of tumor types and can silence tumor suppressor genes and, therefore, is important for carcinogenesis. Although hypoxia is recognized to be an adverse factor in tumor growth and metastasis, the role of G9a in regulating gene expression in hypoxia has not been described extensively. Here, we show that G9a protein stability is increased in hypoxia via reduced proline hydroxylation and, hence, inefficient degradation by the proteasome...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28627341/-protective-effects-of-valproic-acid-on-gut-barrier-function-after-major-burn-injury-and-its-mechanism
#20
Hongmin Luo, Sen Hu, Huining Bian, Shaoyi Zheng, Bing Xiong, Zhifeng Huang, Zuan Liu, Chuanwei Sun, Lianghua Ma, Hanhua Li, Wen Yu, Minghua Du, Huade Chen, Wen Lai
OBJECTIVE: To investigate the potential protective effects of valproic acid (VPA) on gut barrier function after major burn injury in rats and its mechanism. METHODS: Forty male Sprague-Dawley (SD) rats were divided into sham + normal saline (NS), sham + VPA, scald + NS, and scald + VPA groups, with 10 rats in each group. Rat with 55% total body surface area (TBSA) third-degree severe-burns model was reproduced by immersing into 80 °C water, and the rats in sham groups were given sham-burns by immersing into 37 °C water...
March 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
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