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https://www.readbyqxmd.com/read/28923965/sirt7-promotes-adipogenesis-in-the-mouse-by-inhibiting-autocatalytic-activation-of-sirt1
#1
Jian Fang, Alessandro Ianni, Christian Smolka, Olesya Vakhrusheva, Hendrik Nolte, Marcus Krüger, Astrid Wietelmann, Nicolas G Simonet, Juan M Adrian-Segarra, Alejandro Vaquero, Thomas Braun, Eva Bober
Sirtuins (Sirt1-Sirt7) are NAD(+)-dependent protein deacetylases/ADP ribosyltransferases, which play decisive roles in chromatin silencing, cell cycle regulation, cellular differentiation, and metabolism. Different sirtuins control similar cellular processes, suggesting a coordinated mode of action but information about potential cross-regulatory interactions within the sirtuin family is still limited. Here, we demonstrate that Sirt1 requires autodeacetylation to efficiently deacetylate targets such as p53, H3K9, and H4K16...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28916365/sodium-phenylbutyrate-abrogates-african-swine-fever-virus-replication-by-disrupting-the-virus-induced-hypoacetylation-status-of-histone-h3k9-k14
#2
Gonçalo Frouco, Ferdinando B Freitas, Carlos Martins, Fernando Ferreira
African swine fever virus (ASFV) causes a highly lethal disease in swine for which neither a vaccine nor treatment are available. Recently, a new class of drugs that inhibit histone deacetylases enzymes (HDACs) has received an increasing interest as antiviral agents. Considering studies by others showing that valproic acid, an HDAC inhibitor (HDACi), blocks the replication of enveloped viruses and that ASFV regulates the epigenetic status of the host cell by promoting heterochromatinization and recruitment of class I HDACs to viral cytoplasmic factories, the antiviral activity of four HDACi against ASFV was evaluated in this study...
September 13, 2017: Virus Research
https://www.readbyqxmd.com/read/28912063/differential-expression-by-chromatin-modifications-of-alcohol-dehydrogenase-1-of-chorispora-bungeana-in-cold-stress
#3
Lijun Liu, Yuan Song, Jun Xu, Dongming Li, Gaopeng Li, Lizhe An
Epigenetic modifications regulate plant genes to cope with a variety of environmental stresses. Chorispora bungeana is an alpine subnival plant with strong tolerance to multiple abiotic stresses, especially cold stress. In this study, we characterized the alcohol dehydrogenase 1 gene from Chorispora bungeana, CbADH1, that is up-regulated in cold conditions. Overexpression of CbADH1 in Arabidopsis thaliana improved cold tolerance, as indicated by a decreased lethal temperature (LT50). Chromatin immunoprecipitation assays showed that histone H3 is removed from the promoter region and the middle-coding region of the gene...
September 11, 2017: Gene
https://www.readbyqxmd.com/read/28890349/molecular-hydrogen-modulates-gene-expression-via-histone-modification-and-induces-the-mitochondrial-unfolded-protein-response
#4
Sayaka Sobue, Chisato Inoue, Fumiko Hori, Shanlou Qiao, Takashi Murate, Masatoshi Ichihara
Molecular hydrogen (H2) is a biologically active gas that is used medically to ameliorate various systemic pathological conditions. H2 also regulates gene expression involved in intracellular signaling and metabolic pathways. However, it is unclear whether H2 affects gene expression directly or through indirect effects as a consequence of health improvement. Therefore, we attempted to identify genes that exhibit similar changes in expression in response to H2 by employing DNA microarrays and gene set enrichment analysis to analyze RNA from liver and lung of rats and mice with or without dietary stress...
September 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28890329/histone-methyltransferase-setdb1-maintains-survival-of-mouse-spermatogonial-stem-progenitor-cells-via-pten-akt-foxo1-pathway
#5
Tiantian Liu, Xiaoxu Chen, Tianjiao Li, Xueliang Li, Yinghua Lyu, Xiaoteng Fan, Pengfei Zhang, Wenxian Zeng
Spermatogonial stem cells (SSCs) possess the capacity of self-renewal and differentiation, which are the basis of spermatogenesis. In maintenance of SSC homeostasis, intrinsic/extrinsic factors and various signaling pathways tightly control the fate of SSCs. Methyltransferase SETDB1 (Set domain, bifurcated 1) catalyzes histone H3 lysine 9 (H3K9) trimethylation and represses gene expression. SETDB1 is required for maintaining the survival of spermatogonial stem cells in mice. However, the underlying molecular mechanism remains unclear...
September 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28887438/-silencing-of-retrotransposons-by-setdb1-inhibits-the-interferon-response-in-acute-myeloid-leukemia
#6
Trinna L Cuellar, Anna-Maria Herzner, Xiaotian Zhang, Yogesh Goyal, Colin Watanabe, Brad A Friedman, Vasantharajan Janakiraman, Steffen Durinck, Jeremy Stinson, David Arnott, Tommy K Cheung, Subhra Chaudhuri, Zora Modrusan, Jonas Martin Doerr, Marie Classon, Benjamin Haley
A propensity for rewiring genetic and epigenetic regulatory networks, thus enabling sustained cell proliferation, suppression of apoptosis, and the ability to evade the immune system, is vital to cancer cell propagation. An increased understanding of how this is achieved is critical for identifying or improving therapeutic interventions. In this study, using acute myeloid leukemia (AML) human cell lines and a custom CRISPR/Cas9 screening platform, we identify the H3K9 methyltransferase SETDB1 as a novel, negative regulator of innate immunity...
September 8, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28887033/long-term-exposure-to-pm2-5-lowers-influenza-virus-resistance-via-down-regulating-pulmonary-macrophage-kdm6a-and-mediates-histones-modification-in-il-6-and-ifn-%C3%AE-promoter-regions
#7
Jing-Hui Ma, Shao-Hua Song, Meng Guo, Ji Zhou, Fang Liu, Li Peng, Zhi-Ren Fu
Atmospheric particulates, especially PM2.5, not only damage the respiratory system, but also play important roles in pulmonary immunity. China is influenced by atmospheric diffusion conditions, industrial manufacturers, and heating and discharging. PM2.5 levels in the air rise substantially in the winter, which is also a period of flu high-incidence. Although an epidemiological link exists between PM2.5 and flu, we do not understand how long-term PM2.5 inhalation affects pulmonary immunity and the influenza virus response...
September 5, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28886131/histone-deacetylase-regulates-insulin-signaling-via-two-pathways-in-pancreatic-%C3%AE-cells
#8
Yukina Kawada, Shun-Ichiro Asahara, Yumiko Sugiura, Ayaka Sato, Ayuko Furubayashi, Mao Kawamura, Alberto Bartolome, Emi Terashi-Suzuki, Tomoko Takai, Ayumi Kanno, Maki Koyanagi-Kimura, Tomokazu Matsuda, Naoko Hashimoto, Yoshiaki Kido
Recent studies demonstrated that insulin signaling plays important roles in the regulation of pancreatic β cell mass, the reduction of which is known to be involved in the development of diabetes. However, the mechanism underlying the alteration of insulin signaling in pancreatic β cells remains unclear. The involvement of epigenetic control in the onset of diabetes has also been reported. Thus, we analyzed the epigenetic control of insulin receptor substrate 2 (IRS2) expression in the MIN6 mouse insulinoma cell line...
2017: PloS One
https://www.readbyqxmd.com/read/28879500/in-silico-probing-and-biological-evaluation-of-setdb1-eset-targeted-novel-compounds-that-reduce-tri-methylated-histone-h3k9-h3k9me3-level
#9
Insun Park, Yu Jin Hwang, TaeHun Kim, Ambily Nath Indu Viswanath, Ashwini M Londhe, Seo Yun Jung, Kyoung Mi Sim, Sun-Joon Min, Ji Eun Lee, Jihye Seong, Yun Kyung Kim, Kyoung Tai No, Hoon Ryu, Ae Nim Pae
ERG-associated protein with the SET domain (ESET/SET domain bifurcated 1/SETDB1/KMT1E) is a histone lysine methyltransferase (HKMT) and it preferentially tri-methylates lysine 9 of histone H3 (H3K9me3). SETDB1/ESET leads to heterochromatin condensation and epigenetic gene silencing. These functional changes are reported to correlate with Huntington's disease (HD) progression and mood-related disorders which make SETDB1/ESET a viable drug target. In this context, the present investigation was performed to identify novel peptide-competitive small molecule inhibitors of the SETDB1/ESET by a combined in silico-in vitro approach...
September 6, 2017: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/28878090/histone-3-lysine-9-acetylation-is-a-biomarker-of-the-effects-of-culture-on-zygotes
#10
C Rollo, Y Li, X L Jin, C O'Neill
Acetylation of histone proteins is a major determinant of chromatin structure and function. Fertilisation triggers a round of chromatin remodelling that prepares the genome for the first round of transcription from the new embryonic genome. In this study we confirm that fertilisation leads to a marked progressive increase in the level of histone 3 lysine 9 acetylation in both the paternally and maternally derived genomes. The culture of zygotes in simple defined media caused a marked increase in the global level of acetylation and this affected the male pronucleus more than the female...
October 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28874256/correction-%C3%A2-impact-of-nucleic-acid-and-methylated-h3k9-binding-activities-of-suv39h1-on-its-heterochromatin-assembly
#11
Atsuko Shirai, Takayuki Kawaguchi, Hideaki Shimojo, Daisuke Muramatsu, Mayumi Ishida-Yonetani, Yoshifumi Nishimura, Hiroshi Kimura, Jun-Ichi Nakayama, Yoichi Shinkai
No abstract text is available yet for this article.
September 6, 2017: ELife
https://www.readbyqxmd.com/read/28871079/sirt6-deficiency-exacerbates-podocyte-injury-and-proteinuria-through-targeting-notch-signaling
#12
Min Liu, Kaili Liang, Junhui Zhen, Meng Zhou, Xiaojie Wang, Ziying Wang, Xinbing Wei, Yan Zhang, Yu Sun, Zhuanli Zhou, Hua Su, Chun Zhang, Ningjun Li, Chengjiang Gao, Jun Peng, Fan Yi
Podocyte injury is a major determinant of proteinuric kidney disease and the identification of potential therapeutic targets for preventing podocyte injury has clinical importance. Here, we show that histone deacetylase Sirt6 protects against podocyte injury through epigenetic regulation of Notch signaling. Sirt6 is downregulated in renal biopsies from patients with podocytopathies and its expression correlates with glomerular filtration rate. Podocyte-specific deletion of Sirt6 exacerbates podocyte injury and proteinuria in two independent mouse models, diabetic nephropathy, and adriamycin-induced nephropathy...
September 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28860594/sirt6-promotes-osteogenic-differentiation-of-mesenchymal-stem-cells-through-bmp-signaling
#13
Ping Zhang, Yunsong Liu, Yuejun Wang, Min Zhang, Longwei Lv, Xiao Zhang, Yongsheng Zhou
SIRT6 has been identified as an H3K9 deacetylase and a critical regulator of genome stability, telomere integrity, and metabolic homeostasis. Sirt6-deficient mice displayed dramatic phenotypes including profound lymphopenia, loss of subcutaneous fat, lordokyphosis and low bone marrow density. Here, we report that SIRT6 regulates osteogenic differentiation independent of its deacetylase activity in vitro. Further mechanistic studies showed that SIRT6 involves the cell fate determination by modulating bone morphogenetic protein (BMP) signaling...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28851851/multifunctional-involvement-of-a-c2h2-zinc-finger-protein-pbzfp-in-malaria-transmission-histone-modification-and-susceptibility-to-dna-damage-response
#14
Anusha M Gopalakrishnan, Ahmed S I Aly, L Aravind, Nirbhay Kumar
In sexually reproducing organisms, meiosis is an essential step responsible for generation of haploid gametes from diploid somatic cells. The quest for understanding regulatory mechanisms of meiotic recombination in Plasmodium led to identification of a gene encoding a protein that contains 11 copies of C2H2 zinc fingers (ZnF). Reverse genetic approaches were used to create Plasmodium berghei parasites either lacking expression of full-length Plasmodium berghei zinc finger protein (PbZfp) (knockout [KO]) or expressing PbZfp lacking C-terminal zinc finger region (truncated [Trunc])...
August 29, 2017: MBio
https://www.readbyqxmd.com/read/28843785/hif-1%C3%AE-coordinates-epigenetic-activation-of-siah1-in-hepatocytes-in-response-to-nutritional-stress
#15
Zhiwen Fan, Zilong Li, Yuyu Yang, Shuai Liu, Junli Guo, Yong Xu
Hypoxia inducible factor 1 alpha (HIF-1α) regulates a diverse range of pathophysiological processes. It has been demonstrated previously that HIF-1α plays a role in the pathogenesis of steatosis mediating the effects of excessive nutritional insults. In the present study we investigated the role of HIF-1α in trans‑activating the seven in absentia homolog 1 (SIAH1) gene and the underlying mechanism. We report that in response to nutritional stress, SIAH1 expression was up-regulated in the liver in mice and in cultured hepatocytes...
August 24, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28840369/novel-histone-deacetylase-8-selective-inhibitor-1-3-4-oxadiazole-alanine-hybrid-induces-apoptosis-in-breast-cancer-cells
#16
Vijaya Rao Pidugu, Nagendra Sastry Yarla, Anupam Bishayee, Arunasree M Kalle, Alapati Krishna Satya
Identification of isoform-specific histone deacetylase inhibitors (HDACi) is a significant advantage to overcome the adverse side effects of pan-HDACi for the treatment of various diseases, including cancer. We have designed, and synthesized novel 1,3,4 oxadiazole with glycine/alanine hybrids as HDAC8-specific inhibitors and preliminary evaluation has indicated that 1,3,4 oxadiazole with alanine hybrid [(R)-2-amino-N-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)propanamide (10b)] to be a potent HDAC8 inhibitor. In the present study, the in vitro efficacy of the molecule in inhibiting the cancer cell proliferation and the underlying molecular mechanism was studied...
August 24, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28826851/jmjd1c-ensures-mouse-embryonic-stem-cell-self-renewal-and-somatic-cell-reprogramming-through-controlling-microrna-expression
#17
Feng Xiao, Bing Liao, Jing Hu, Shuang Li, Haixin Zhao, Ming Sun, Junjie Gu, Ying Jin
The roles of histone demethylases (HDMs) for the establishment and maintenance of pluripotency are incompletely characterized. Here, we show that JmjC-domain-containing protein 1c (JMJD1C), an H3K9 demethylase, is required for mouse embryonic stem cell (ESC) self-renewal. Depletion of Jmjd1c leads to the activation of ERK/MAPK signaling and epithelial-to-mesenchymal transition (EMT) to induce differentiation of ESCs. Inhibition of ERK/MAPK signaling rescues the differentiation phenotype caused by Jmjd1c depletion...
September 12, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28819251/g9a-regulates-breast-cancer-growth-by-modulating-iron-homeostasis-through-the-repression-of-ferroxidase-hephaestin
#18
Ya-Fang Wang, Jie Zhang, Yi Su, Yan-Yan Shen, Dong-Xian Jiang, Ying-Yong Hou, Mei-Yu Geng, Jian Ding, Yi Chen
G9a, a H3K9 methyltransferase, shows elevated expression in many types of human cancers, particularly breast cancer. However, the tumorigenic mechanism of G9a is still far from clear. Here we report that G9a exerts its oncogenic function in breast cancer by repressing hephaestin and destruction cellular iron homeostasis. In the case of pharmacological inhibition or short hairpin RNA interference-mediated suppression of G9a, the expression and activity of hephaestin increases, leading to the observed decrease of intracellular labile iron content and the disturbance of breast cancer cell growth in vitro and in vivo...
August 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28803780/methylation-of-dna-ligase-1-by-g9a-glp-recruits-uhrf1-to-replicating-dna-and-regulates-dna-methylation
#19
Laure Ferry, Alexandra Fournier, Takeshi Tsusaka, Guillaume Adelmant, Tadahiro Shimazu, Shohei Matano, Olivier Kirsh, Rachel Amouroux, Naoshi Dohmae, Takehiro Suzuki, Guillaume J Filion, Wen Deng, Maud de Dieuleveult, Lauriane Fritsch, Srikanth Kudithipudi, Albert Jeltsch, Heinrich Leonhardt, Petra Hajkova, Jarrod A Marto, Kyohei Arita, Yoichi Shinkai, Pierre-Antoine Defossez
DNA methylation is an essential epigenetic mark in mammals that has to be re-established after each round of DNA replication. The protein UHRF1 is essential for this process; it has been proposed that the protein targets newly replicated DNA by cooperatively binding hemi-methylated DNA and H3K9me2/3, but this model leaves a number of questions unanswered. Here, we present evidence for a direct recruitment of UHRF1 by the replication machinery via DNA ligase 1 (LIG1). A histone H3K9-like mimic within LIG1 is methylated by G9a and GLP and, compared with H3K9me2/3, more avidly binds UHRF1...
August 17, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28790329/kdm4b-mediated-reduction-of-h3k9me3-and-h3k36me3-levels-improves-somatic-cell-reprogramming-into-pluripotency
#20
Jingwei Wei, Jisha Antony, Fanli Meng, Paul MacLean, Rebekah Rhind, Götz Laible, Björn Oback
Correct reprogramming of epigenetic marks is essential for somatic cells to regain pluripotency. Repressive histone (H) lysine (K) methylation marks are known to be stable and difficult to reprogram. In this study, we generated transgenic mice and mouse embryonic fibroblasts (MEFs) for the inducible expression of KDM4B, a demethylase that removes H3 K9 and H3K36 trimethylation (me3) marks (H3K9/36me3). Upon inducing Kdm4b, H3K9/36me3 levels significantly decreased compared to non-induced controls. Concurrently, H3K9me1 levels significantly increased, while H3K9me2 and H3K27me3 remained unchanged...
August 8, 2017: Scientific Reports
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