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https://www.readbyqxmd.com/read/28231240/galectin-3-histone-deacetylases-and-hedgehog-signaling-possible-convergent-targets-in-schistosomiasis-induced-liver-fibrosis
#1
REVIEW
Felipe Leite de Oliveira, Katia Carneiro, José Marques Brito, Mariana Cabanel, Jonathas Xavier Pereira, Ligia de Almeida Paiva, Wingkin Syn, Neil C Henderson, Marcia Cury El-Cheikh
Schistosomiasis affects approximately 240 million people in the world. Schistosoma mansoni eggs in the liver induce periportal fibrosis and hepatic failure driven by monocyte recruitment and macrophage activation, resulting in robust Th2 response. Here, we suggested a possible involvement of Galectin-3 (Gal-3), histone deacetylases (HDACs), and Hedgehog (Hh) signaling with macrophage activation during Th1/Th2 immune responses, fibrogranuloma reaction, and tissue repair during schistosomiasis. Gal-3 is highly expressed by liver macrophages (Kupffer cells) around Schistosoma eggs...
February 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28230854/opposite-effects-of-hdac5-and-p300-on-mrtf-a-related-neuronal-apoptosis-during-ischemia-reperfusion-injury-in-rats
#2
Na Li, Qiong Yuan, Xiao-Lu Cao, Ying Zhang, Zhen-Li Min, Shi-Qiang Xu, Zhi-Jun Yu, Jing Cheng, Chunxiang Zhang, Xia-Min Hu
Our recent study has revealed that the myocardin-related transcription factor-A (MRTF-A) is involved in the apoptosis of cortical neurons induced by ischemia/reperfusion (I/R). Histone deacetylase 5 (HDAC5) and histone acetyltransferase p300 (P300) are two well-known regulators for transcription factors; however, their roles in MRTF-A-related effect on neuronal injuries during I/R are still unclear. In this study, in a model rat cerebral I/R injury via middle cerebral artery occlusion and reperfusion, we found that the expression and activity of HDAC5 was upregulated, whereas p300 and MRTF-A were downregulated both in expression and activity during I/R...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230635/valproic-acid-modulates-platelet-and-coagulation-function-ex-vivo
#3
Ted Bambakidis, Simone E Dekker, Ihab Halaweish, Baoling Liu, Vahagn C Nikolian, Patrick E Georgoff, Patryk Piascik, Yongqing Li, Martin Sillesen, Hasan B Alam
Trauma-induced coagulopathy is associated with adverse patient outcome. Animal models demonstrate that histone deacetylase inhibitors, such as valproic acid (VPA), improve survival following injury. While in-vivo data suggest that improved survival may in part be because of an attenuation of coagulopathy, it remains unknown whether this is a direct effect of the drug, or the establishment of an overall prosurvival phenotype. We thus conducted an ex-vivo experiment to determine if VPA has an effect on coagulation and platelet function...
February 21, 2017: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
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
#4
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/28229975/diverse-roles-of-wdr5-rbbp5-ash2l-dpy30-wrad-complex-in-the-functions-of-the-set1-histone-methyltransferase-family
#5
Aamir Ali, Shweta Tyagi
WD repeat containing protein 5 (WDR5), Retinoblastoma Binding Protein 5 (RbBP5), Absent-Small-Homeotic-2- Like protein (ASH2L), and Dumpy-30 (Dpy30) have been reported to be the integral and shared components of all the SET1 family of histone 3 lysine 4 histone methyltransferase (HMT) complexes. Collectively called the WRAD complex, these proteins are pivotal to the HMT activity of the SET1 complexes. Recent reports highlight the novel non-canonical functions of WRAD in cellular processes other than its well-studied role in histone methylation and gene expression...
March 2017: Journal of Biosciences
https://www.readbyqxmd.com/read/28229965/atmbd6-a-methyl-cpg-binding-domain-protein-maintains-gene-silencing-in-arabidopsis-by-interacting-with-rna-binding-proteins
#6
Adwaita Prasad Parida, Amrapali Sharma, Arun Kumar Sharma
DNA methylation, mediated by double-stranded RNA, is a conserved epigenetic phenomenon that protects a genome from transposons, silences unwanted genes and has a paramount function in plant or animal development. Methyl CpG binding domain proteins are members of a class of proteins that bind to methylated DNA. The Arabidopsis thaliana genome encodes 13 methyl CpG binding domain (MBD) proteins, but the molecular/biological functions of most of these proteins are still not clear. In the present study, we identified four proteins that interact with AtMBD6...
March 2017: Journal of Biosciences
https://www.readbyqxmd.com/read/28229514/mutations-in-genes-encoding-polycomb-repressive-complex-2-subunits-cause-weaver-syndrome
#7
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/28229434/preclinical-pharmacokinetics-and-pharmacodynamics-of-pinometostat-epz-5676-a-first-in-class-small-molecule-s-adenosyl-methionine-competitive-inhibitor-of-dot1l
#8
Nigel J Waters
Acute leukemias bearing mixed lineage leukemia (MLL) rearrangements are aggressive diseases characterized by a poor overall prognosis despite multi-agent chemotherapy. Aberrant fusion proteins involving the MLL histone methyltransferase (HMT) lead to recruitment of DOT1L, to a multi-protein complex resulting in aberrant methylation of histone H3 lysine 79 at MLL target genes, and ultimately enhanced expression of critical genes for hematopoietic differentiation, including HOXA9 and MEIS1, and as such defines the established mechanism for leukemogenesis in MLL-rearrangement (MLL-r) leukemias...
February 22, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28228846/decoupling-the-downstream-effects-of-germline-nuclear-rnai-reveals-that-h3k9me3-is-dispensable-for-heritable-rnai-and-the-maintenance-of-endogenous-sirna-mediated-transcriptional-silencing-in-caenorhabditis-elegans
#9
Natallia Kalinava, Julie Zhouli Ni, Kimberly Peterman, Esteban Chen, Sam Guoping Gu
BACKGROUND: Germline nuclear RNAi in C. elegans is a transgenerational gene-silencing pathway that leads to H3K9 trimethylation (H3K9me3) and transcriptional silencing at the target genes. H3K9me3 induced by either exogenous double-stranded RNA (dsRNA) or endogenous siRNA (endo-siRNA) is highly specific to the target loci and transgenerationally heritable. Despite these features, the role of H3K9me3 in siRNA-mediated transcriptional silencing and inheritance of the silencing state at native target genes is unclear...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28228845/histone-and-dna-methylation-control-by-h3-serine-10-threonine-11-phosphorylation-in-the-mouse-zygote
#10
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/28228757/regulation-of-epigenetic-modifiers-including-kdm6b-by-interferon-%C3%AE-and-interleukin-4-in-human-macrophages
#11
Gökçe Yıldırım-Buharalıoğlu, Mark Bond, Graciela B Sala-Newby, Charles C T Hindmarch, Andrew C Newby
BACKGROUND: Interferon-γ (IFN-γ) or interleukin-4 (IL-4) drives widely different transcriptional programs in macrophages. However, how IFN-γ and IL-4 alter expression of histone-modifying enzymes involved in epigenetic regulation and how this affects the resulting phenotypic polarization is incompletely understood. METHODS AND RESULTS: We investigated steady-state messenger RNA levels of 84 histone-modifying enzymes and related regulators in colony-stimulating factor-1 differentiated primary human macrophages using quantitative polymerase chain reaction...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28228717/mild-hypothermia-attenuates-the-anesthetic-isoflurane-induced-cytotoxicity
#12
Cheng Li, Yuanlin Dong, Dan Chen, Zhongcong Xie, Yiying Zhang
The commonly used inhalation anesthetic isoflurane has been reported to induce DNA damage and cytotoxicity. However, the methods to attenuate these effects remain largely to be determined. Mild hypothermia has neuroprotective effects. We therefore set out to assess whether mild hypothermia could protect the isoflurane-induced DNA damage and cytotoxicity. Moreover, we investigated the underlying mechanisms by assessing the effects of mild hypothermia on the isoflurane-induced changes in ATP levels. H4 human neuroglioma cells were treated with 2% isoflurane for 3 or 6 h with and without mild hypothermia (35°C)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28228401/wolf-hirschhorn-syndrome-candidate-1-like-1-epigenetically-regulates-nephrin-gene-expression
#13
Yugo Ito, Kan Katayama, Yukino Nishibori, Yoshihiro Akimoto, Akihiko Kudo, Ryota Kurayama, Ichiro Hada, Shohei Takahashi, Toru Kimura, Toshiyuki Fukutomi, Tomohisa Katada, Junichi Suehiro, Olga Beltcheva, Karl Tryggvason, Kunimasa Yan
Altered expression of nephrin underlies the pathophysiology of proteinuria in both congenital and acquired nephrotic syndrome. However, the epigenetic mechanisms of nephrin gene regulation remain elusive. Here, we show that Wolf-Hirschhorn syndrome candidate 1-like 1 long form (WHSC1L1-L) is a novel epigenetic modifier of nephrin gene regulation. WHSC1L1-L was associated with histone H3K4 and H3K36 in human embryonic kidney cells. WHSC1L1-L gene was expressed in the podocytes and functional protein product was detected in these cells...
February 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28228264/lsd1-controls-timely-myod-expression-via-myod-core-enhancer-transcription
#14
Isabella Scionti, Shinichiro Hayashi, Sandrine Mouradian, Emmanuelle Girard, Joana Esteves de Lima, Véronique Morel, Thomas Simonet, Maud Wurmser, Pascal Maire, Katia Ancelin, Eric Metzger, Roland Schüle, Evelyne Goillot, Frederic Relaix, Laurent Schaeffer
MyoD is a master regulator of myogenesis. Chromatin modifications required to trigger MyoD expression are still poorly described. Here, we demonstrate that the histone demethylase LSD1/KDM1a is recruited on the MyoD core enhancer upon muscle differentiation. Depletion of Lsd1 in myoblasts precludes the removal of H3K9 methylation and the recruitment of RNA polymerase II on the core enhancer, thereby preventing transcription of the non-coding enhancer RNA required for MyoD expression (CEeRNA). Consistently, Lsd1 conditional inactivation in muscle progenitor cells during embryogenesis prevented transcription of the CEeRNA and delayed MyoD expression...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228258/clonal-expansion-of-lgr5-positive-cells-from-mammalian-cochlea-and-high-purity-generation-of-sensory-hair-cells
#15
Will J McLean, Xiaolei Yin, Lin Lu, Danielle R Lenz, Dalton McLean, Robert Langer, Jeffrey M Karp, Albert S B Edge
Death of cochlear hair cells, which do not regenerate, is a cause of hearing loss in a high percentage of the population. Currently, no approach exists to obtain large numbers of cochlear hair cells. Here, using a small-molecule approach, we show significant expansion (>2,000-fold) of cochlear supporting cells expressing and maintaining Lgr5, an epithelial stem cell marker, in response to stimulation of Wnt signaling by a GSK3β inhibitor and transcriptional activation by a histone deacetylase inhibitor...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228253/sirt6-suppresses-cancer-stem-like-capacity-in-tumors-with-pi3k-activation-independently-of-its-deacetylase-activity
#16
Rafael M Ioris, Mirco Galié, Giorgio Ramadori, Jason G Anderson, Anne Charollais, Georgia Konstantinidou, Xavier Brenachot, Ebru Aras, Algera Goga, Nicholas Ceglia, Carlos Sebastián, Denis Martinvalet, Raul Mostoslavsky, Pierre Baldi, Roberto Coppari
Cancer stem cells (CSCs) have high tumorigenic capacity. Here, we show that stem-like traits of specific human cancer cells are reduced by overexpression of the histone deacetylase sirtuin 6 (SIRT6). SIRT6-sensitive cancer cells bear mutations that activate phosphatidylinositol-3-kinase (PI3K) signaling, and overexpression of SIRT6 reduces growth, progression, and grade of breast cancer in a mouse model with PI3K activation. Tumor metabolomic and transcriptomic analyses reveal that SIRT6 overexpression dampens PI3K signaling and stem-like characteristics and causes metabolic rearrangements in this cancer model...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228067/epigenetic-characteristics-of-the-mitotic-chromosome-in-1d-and-3d
#17
Marlies E Oomen, Job Dekker
While chromatin characteristics in interphase are widely studied, characteristics of mitotic chromatin and their inheritance through mitosis are still poorly understood. During mitosis, chromatin undergoes dramatic changes: transcription stalls, chromatin-binding factors leave the chromatin, histone modifications change and chromatin becomes highly condensed. Many key insights into mitotic chromosome state and conformation have come from extensive microscopy studies over the last century. Over the last decade, the development of 3C-based techniques has enabled the study of higher order chromosome organization during mitosis in a genome-wide manner...
April 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28226269/the-causes-and-consequences-of-dna-methylome-variation-in-plants
#18
REVIEW
Danelle K Seymour, Claude Becker
Epigenetic variation - polymorphisms at the level of DNA methylation or histone modifications - modulates chromatin accessibility, which can perturb transcriptional activity and spur phenotypic variation. Determining the origin, frequency spectrum, and consequences of epigenetic variants is key to understanding the role of this variation in generating stable phenotypic variation in plants. Here we review recent literature on DNA methylation variation in both model and crop plant species with a focus on the link between genotype, epigenotype, and transcription...
February 19, 2017: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/28225782/chronic-treatment-of-non-small-cell-lung-cancer-cells-with-gefitinib-leads-to-an-epigenetic-loss-of-epithelial-properties-associated-with-reductions-in-microrna-155-and-200c
#19
Michiko Narita, Eri Shimura, Atsumi Nagasawa, Toshiki Aiuchi, Yukari Suda, Yusuke Hamada, Daigo Ikegami, Chizuru Iwasawa, Kazuhiko Arakawa, Katsuhide Igarashi, Naoko Kuzumaki, Yusuke Yoshioka, Takahiro Ochiya, Hideyuki Takeshima, Toshikazu Ushijima, Minoru Narita
BACKGROUND: The EGFR tyrosine kinase inhibitor gefitinib is used in therapy for non-small-cell lung cancer (NSCLC). However, its application is limited by resistance-accelerated disease progression, which is accompanied by the epithelial-to-mesenchymal transition (EMT). In the present study, we performed multiple expression analyses of microRNAs (miRNAs) and quantified the expression of several related EMT players in gefitinib-resistant NSCLC cells. METHODS AND RESULTS: To establish gefitinib-resistant NSCLC cells, gefitinib-sensitive HCC827 cells, which exhibit an in-frame deletion [E746-A750] in EGFR exon 19, were exposed to gefitinib for at least 1...
2017: PloS One
https://www.readbyqxmd.com/read/28225203/identification-of-interacting-proteins-of-the-tafve-protein-involved-in-spike-development-in-bread-wheat
#20
Yong-Sheng Zheng, Yu-Qing Lu, Ying-Ying Meng, Rong-Zhi Zhang, Han Zhang, Jia-Mei Sun, Mu-Mu Wang, Li-Hui Li, Ru-Yu Li
FVE/MSI4 plays important roles in determining flowering time in Arabidopsis. However, its function is unexplored in wheat. In the present study, Co-IP and nano-LC-MS/MS were used to identify TaFVE-interacting or associated proteins. Altogether 89 differentially expressed proteins showed the same down-regulated expression trends as TaFVE in wheat line 5660M. Among them, 62 proteins were further predicted to be involved in the interaction network of TaFVE and 11 proteins have been shown to be potential TaFVE interactors based on curated databases and experimentally determined in other species by the STRING...
February 22, 2017: Proteomics
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