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https://www.readbyqxmd.com/read/27906114/p38%C3%AE-mapk-disables-kmt1a-mediated-repression-of-myogenic-differentiation-program
#1
Biswanath Chatterjee, David W Wolff, Mathivanan Jothi, Munmun Mal, Asoke K Mal
BACKGROUND: Master transcription factor MyoD can initiate the entire myogenic gene expression program which differentiates proliferating myoblasts into multinucleated myotubes. We previously demonstrated that histone methyltransferase KMT1A associates with and inhibits MyoD in proliferating myoblasts, and must be removed to allow differentiation to proceed. It is known that pro-myogenic signaling pathways such as PI3K/AKT and p38α MAPK play critical roles in enforcing associations between MyoD and transcriptional activators, while removing repressors...
August 22, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27906051/the-lysine-methyltransferase-ehmt2-g9a-is-dispensable-for-skeletal-muscle-development-and-regeneration
#2
Regan-Heng Zhang, Robert N Judson, David Y Liu, Jürgen Kast, Fabio M V Rossi
BACKGROUND: Euchromatic histone-lysine N-methyltransferase 2 (G9a/Ehmt2) is the main enzyme responsible for the apposition of H3K9 di-methylation on histones. Due to its dual role as an epigenetic regulator and in the regulation of non-histone proteins through direct methylation, G9a has been implicated in a number of biological processes relevant to cell fate control. Recent reports employing in vitro cell lines indicate that Ehmt2 methylates MyoD to repress its transcriptional activity and therefore its ability to induce differentiation of activated myogenic cells...
May 27, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27903908/ing1-regulates-rrna-levels-by-altering-nucleolar-chromatin-structure-and-mtor-localization
#3
Uma Karthika Rajarajacholan, Subhash Thalappilly, Karl Riabowol
Epigenetic, transcriptional and signaling processes in the nucleolus regulate rRNA transcription and cell growth. We report here that the tumor suppressor ING1b binds rDNA, regulates rDNA chromatin modifications and affects nucleolar localization of mTOR to modulate rRNA levels. ING1 represses rDNA transcription by recruiting HDAC1 to rDNA loci, increasing its association with the NoRC complex and deacetylating the histone H3K9 and H3K27 marks of active transcription. Loss of ING1 enhances nucleolar localization of phospho-mTOR and its association with Raptor and GβL, even during rapamycin treatment...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27900099/effect-of-cytostatic-proline-rich-polypeptide-1-on-tumor-suppressors-of-inflammation-pathway-signaling-in-chondrosarcoma
#4
Karina Galoian, Shihua Luo, Amir Qureshi, Parthik Patel, Rachel Price, Ashlyn S Morse, Gor Chailyan, Silva Abrahamyan, H T Temple
Cytokines produced in the tumour microenvironment exert an important role in cancer pathogenesis and in the inhibition of disease progression. Cancer of the cartilage is termed metastatic chondrosarcoma; however, the signaling events resulting in mesenchymal cell transformation to sarcoma have yet to be fully elucidated. The present study aimed to characterize the cytokine expression profile in the human JJ012 chondrosarcoma cell line, as well as the effect of cytostatic proline-rich polypeptide-1 (PRP-1). Western blot experiments demonstrated that the levels of suppressor of cytokine signaling 3 (SOCS3) were upregulated in chondrocytes compared with chondrosarcoma cells...
November 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/27894088/lsd1-binds-to-hpv16-e7-and-promotes-the-epithelial-mesenchymal-transition-in-cervical-cancer-by-demethylating-histones-at-the-vimentin-promoter
#5
Yuan Liu, Yanan Wang, Chunqin Chen, Jiawen Zhang, Wenyan Qian, Yu Dong, Zhiqiang Liu, Xi Zhang, Xiaoyun Wang, Zhenbo Zhang, Xiaobing Shi, Sufang Wu
Lysine-specific demethylase 1 (LSD1), which specifically demethylates histone H3 lysine 4 (H3K4) and lysine 9 (H3K9), is dysregulated in several cancers. We found that ectopic expression of LSD1 in cervical cancer cells promoted invasion and metastasis in vitro and in vivo, reduced the expression of the epithelial marker E-cadherin, and induced the expression of the mesenchymal marker, Vimentin. By contrast, LSD1 knockdown had the opposite effect and attenuated the HPV16 E7-induced epithelial-mesenchymal transition (EMT)...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27893464/the-h3k9-dimethyltransferases-ehmt1-2-protect-against-pathological-cardiac-hypertrophy
#6
Bernard Thienpont, Jan Magnus Aronsen, Emma Louise Robinson, Hanneke Okkenhaug, Elena Loche, Arianna Ferrini, Patrick Brien, Kanar Alkass, Antonio Tomasso, Asmita Agrawal, Olaf Bergmann, Ivar Sjaastad, Wolf Reik, Hywel Llewelyn Roderick
Cardiac hypertrophic growth in response to pathological cues is associated with reexpression of fetal genes and decreased cardiac function and is often a precursor to heart failure. In contrast, physiologically induced hypertrophy is adaptive, resulting in improved cardiac function. The processes that selectively induce these hypertrophic states are poorly understood. Here, we have profiled 2 repressive epigenetic marks, H3K9me2 and H3K27me3, which are involved in stable cellular differentiation, specifically in cardiomyocytes from physiologically and pathologically hypertrophied rat hearts, and correlated these marks with their associated transcriptomes...
November 28, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27889685/a-naturally-occurring-mixture-of-tocotrienols-inhibits-the-growth-of-human-prostate-tumor-associated-with-epigenetic-modifications-of-cyclin-dependent-kinase-inhibitors-p21-and-p27
#7
Ying Huang, Renyi Wu, Zheng-Yuan Su, Yue Guo, Xi Zheng, Chung S Yang, Ah-Ng Kong
Tocotrienols, members of the vitamin E family, have three unsaturated bonds in their side chains. Recently, it has been suggested that the biological effects of tocotrienols may differ from that of tocopherols. Several in vitro studies have shown that tocotrienols have stronger anticancer effects than tocopherols. VCaP cell line used in this study is from a vertebral bone metastasis from a patient with prostate cancer. Eight-week-old male NCr(-/-) nude mice were subcutaneously injected with VCaP-luc cells in matrigel and then administered a tocotrienol mixture for 8 weeks...
November 4, 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/27878240/sirt1-activator-represses-the-transcription-of-tnf%C3%A2-%C3%AE-in-thp%C3%A2-1-cells-of-a-sepsis-model-via-deacetylation-of-h4k16
#8
Guo-Dong Chen, Wei-Dong Yu, Xiao-Ping Chen
Sepsis is a systemic inflammatory response resulting from the excessive production of pro-inflammatory cytokines, including tumor necrosis factor (TNF)‑α. Sirtuin 1 (SirT1) actively deacetylates histone proteins, and facilitates chromatin compaction and gene silencing. In the present study, a cell model of sepsis, comprising lipopolysaccharide (LPS)‑tolerant THP‑1 cells, was used to investigate whether the SirT1 activator, resveratrol, repressed the transcription of TNF‑α. Chromatin immunoprecipitation and real‑time PCR were used to determine the transcription of the TNF‑α promoter...
November 15, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27876670/a-model-of-dynamic-stability-of-h3k9me3-heterochromatin-to-explain-the-resistance-to-reprogramming-of-differentiated-cells
#9
Charly Jehanno, Gilles Flouriot, Pascale Le Goff, Denis Michel
Despite their dynamic nature, certain chromatin marks must be maintained over the long term. This is particulary true for histone 3 lysine 9 (H3K9) trimethylation, that is involved in the maintenance of healthy differentiated cellular states by preventing inappropriate gene expression, and has been recently identified as the most efficient barrier to cellular reprogramming in nuclear transfer experiments. We propose that the capacity of the enzymes SUV39H1/2 to rebind to a minor fraction of their products, either directly or via HP1α/β, contributes to the solidity of this mark through (i) a positive feedback involved in its establishment by the mutual enforcement of H3K9me3 and SUV39H1/2 and then (ii) a negative feedback sufficient to strongly stabilize H3K9me3 heterochromatin in post-mitotic cells by generating local enzyme concentrations capable of counteracting transient bursts of demethylation...
November 20, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27869162/the-histone-demethylase-kdm4b-regulates-peritoneal-seeding-of-ovarian-cancer
#10
C Wilson, L Qiu, Y Hong, T Karnik, G Tadros, B Mau, T Ma, Y Mu, J New, R J Louie, S Gunewardena, A K Godwin, O W Tawfik, J Chien, K F Roby, A J Krieg
Epithelial ovarian cancer (EOC) has poor prognosis and rapid recurrence because of widespread dissemination of peritoneal metastases at diagnosis. Multiple pathways contribute to the aggressiveness of ovarian cancer, including hypoxic signaling mechanisms. In this study, we have determined that the hypoxia-inducible histone demethylase KDM4B is expressed in ∼60% of EOC tumors assayed, including primary and matched metastatic tumors. Expression of KDM4B in tumors is positively correlated with expression of the tumor hypoxia marker CA-IX, and is robustly induced in EOC cell lines exposed to hypoxia...
November 21, 2016: Oncogene
https://www.readbyqxmd.com/read/27853364/curcumin-modulates-the-effect-of-histone-modification-on-the-expression-of-chemokines-by-type-ii-alveolar-epithelial-cells-in-a-rat-copd-model
#11
Lixing Gan, Chengye Li, Jian Wang, Xuejun Guo
BACKGROUND: Studies have suggested that histone modification has a positive impact on various aspects associated with the progression of COPD. Histone deacetylase 2 (HDAC2) suppresses proinflammatory gene expression through deacetylation of core histones. OBJECTIVE: To investigate the effect of histone modification on the expression of chemokines in type II alveolar epithelial cells (AEC II) in a rat COPD model and regulation of HDAC2 expression by curcumin in comparison with corticosteroid...
2016: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/27845897/the-jazf1-suz12-fusion-protein-disrupts-prc2-complexes-and-impairs-chromatin-repression-during-human-endometrial-stromal-tumorogenesis
#12
Xianyong Ma, Jinglan Wang, Jianhui Wang, Charles X Ma, Xiaobin Gao, Vytas Patriub, Jeffrey L Sklar
The Polycomb repressive complex 2 (PRC2), which contains three core proteins EZH2, EED and SUZ12, controls chromatin compaction and transcription repression through trimethylation of lysine 27 on histone 3. The (7;17)(p15;q21) chromosomal translocation present in most cases of endometrial stromal sarcomas (ESSs) results in the in-frame fusion of the JAZF1 and SUZ12 genes. We have investigated whether and how the fusion protein JAZF1-SUZ12 functionally alters PRC2. We found that the fusion protein exists at high levels in ESS containing the t(7;17)...
November 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27819724/histone-h3k9-acetylation-influences-growth-characteristics-of-goat-adipose-derived-stem-cells-in-vitro
#13
X Wang, F X Zhang, Z M Wang, Q Wang, H F Wang, Y Ren, D P Tai, H Liang, D J Liu
Adipose-derived stem cells (ADSCs) show nearly unlimited potential in medical and animal science. Currently, understanding of the biological mechanisms regulating ADSC growth in vitro remains very limited. Histone acetylation, an epigenetic modification, plays a key role in maintaining stem cell properties. To further study its effect on ADSC growth characteristics in vitro, we treated goat ADSCs with the histone deacetylase inhibitors trichostatin A (TSA) and vorinostat (SAHA). This inhibited SIRT1 expression and increased histone H3K9 acetylation, leading to decreased cell viability, cell cycle arrest, and apoptosis...
November 3, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27808254/%C3%AE-synuclein-enhances-histone-h3-lysine-9-dimethylation-and-h3k9me2-dependent-transcriptional-responses
#14
Naoto Sugeno, Sandra Jäckel, Aaron Voigt, Zinah Wassouf, Julia Schulze-Hentrich, Philipp J Kahle
α-Synuclein (αS) is a protein linked to Parkinson's disease (PD) and related neurodegenerative disorders. It is mostly localized within synapses, but αS has also been suggested to play a role in the nucleus. We used transgenic Drosophila and inducible SH-SY5Y neuroblastoma cells to investigate the effects of αS on chromatin with a particular focus on histone modifications. Overexpression of αS in male flies as well as in retinoic acid pre-treated neuroblastoma cells led to an elevation of histone H3K9 methylations, mostly mono- (H3K9me1) and di- (H3K9me2)...
November 3, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27807143/hif-kdm3a-mmp12-regulatory-circuit-ensures-trophoblast-plasticity-and-placental-adaptations-to-hypoxia
#15
Damayanti Chakraborty, Wei Cui, Gracy X Rosario, Regan L Scott, Pramod Dhakal, Stephen J Renaud, Makoto Tachibana, M A Karim Rumi, Clifford W Mason, Adam J Krieg, Michael J Soares
The hemochorial placenta develops from the coordinated multilineage differentiation of trophoblast stem (TS) cells. An invasive trophoblast cell lineage remodels uterine spiral arteries, facilitating nutrient flow, failure of which is associated with pathological conditions such as preeclampsia, intrauterine growth restriction, and preterm birth. Hypoxia plays an instructive role in influencing trophoblast cell differentiation and regulating placental organization. Key downstream hypoxia-activated events were delineated using rat TS cells and tested in vivo, using trophoblast-specific lentiviral gene delivery and genome editing...
November 2, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27800642/p110%C3%AE-inhibition-reduces-histone-h3k4-di-methylation-in-prostate-cancer
#16
Jun Pang, Yue-Wu Yang, Yiling Huang, Jun Yang, Hao Zhang, Ruibao Chen, Liang Dong, Yan Huang, Dongying Wang, Jihong Liu, Benyi Li
INTRODUCTION AND AIMS: Epigenetic alteration plays a major role in the development and progression of human cancers, including prostate cancer. Histones are the key factors in modulating gene accessibility to transcription factors and post-translational modification of the histone N-terminal tail including methylation is associated with either transcriptional activation (H3K4me2) or repression (H3K9me3). Furthermore, phosphoinositide 3-kinase (PI3 K) signaling and the androgen receptor (AR) are the key determinants in prostate cancer development and progression...
November 1, 2016: Prostate
https://www.readbyqxmd.com/read/27798683/ubiquitination-of-lysine-867-of-the-human-setdb1-protein-upregulates-its-histone-h3-lysine-9-h3k9-methyltransferase-activity
#17
Kenji Ishimoto, Natsuko Kawamata, Yoshie Uchihara, Moeka Okubo, Reiko Fujimoto, Eiko Gotoh, Keisuke Kakinouchi, Eiichi Mizohata, Nobumasa Hino, Yoshiaki Okada, Yasuhiro Mochizuki, Toshiya Tanaka, Takao Hamakubo, Juro Sakai, Tatsuhiko Kodama, Tsuyoshi Inoue, Keisuke Tachibana, Takefumi Doi
Posttranslational modifications (PTMs) of proteins play a crucial role in regulating protein-protein interactions, enzyme activity, subcellular localization, and stability of the protein. SET domain, bifurcated 1 (SETDB1) is a histone methyltransferase that regulates the methylation of histone H3 on lysine 9 (H3K9), gene silencing, and transcriptional repression. The C-terminal region of SETDB1 is a key site for PTMs, and is essential for its enzyme activity in mammalian and insect cells. In this study, we aimed to evaluate more precisely the effect of PTMs on the H3K9 methyltransferase activity of SETDB1...
2016: PloS One
https://www.readbyqxmd.com/read/27787508/dangerous-r-loops-form-in-the-absence-of-h3k9-methylation
#18
Anna Elisabetta Salcini
Methylation of histone H3 on lysine 9 (H3K9) is a hallmark of transcriptionally inactive heterochromatin that is deregulated in pathological conditions. A new study shows that complete loss of H3K9 methylation in Caenorhabditis elegans leads to derepression of repetitive elements and formation of DNA:RNA hybrids (R loops), resulting in increased rates of repeat-specific mutation.
October 27, 2016: Nature Genetics
https://www.readbyqxmd.com/read/27771437/specific-histone-modifications-play-critical-roles-in-the-control-of-encystation-and-antigenic-variation-in-the-early-branching-eukaryote-giardia-lamblia
#19
Pedro G Carranza, Pablo R Gargantini, César G Prucca, Alessandro Torri, Alicia Saura, Staffan Svärd, Hugo D Lujan
During evolution, parasitic microorganisms have faced the challenges of adapting to different environments to colonize a variety of hosts. Giardia lamblia, a common cause of intestinal disease, has developed fascinating strategies to adapt both outside and inside its host's intestine, such as trophozoite differentiation into cyst and the switching of its major surface antigens. How gene expression is regulated during these adaptive processes remains undefined. Giardia lacks some typical eukaryotic features, like canonical transcription factors, linker histone H1, and complex promoter regions; suggesting that post-transcriptional and translational control of gene expression is essential for parasite survival...
October 19, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27760317/elucidation-of-the-fanconi-anemia-protein-network-in-meiosis-and-its-function-in-the-regulation-of-histone-modifications
#20
Kris G Alavattam, Yasuko Kato, Ho-Su Sin, So Maezawa, Ian J Kowalski, Fan Zhang, Qishen Pang, Paul R Andreassen, Satoshi H Namekawa
Precise epigenetic regulation of the sex chromosomes is vital for the male germline. Here, we analyze meiosis in eight mouse models deficient for various DNA damage response (DDR) factors, including Fanconi anemia (FA) proteins. We reveal a network of FA and DDR proteins in which FA core factors FANCA, FANCB, and FANCC are essential for FANCD2 foci formation, whereas BRCA1 (FANCS), MDC1, and RNF8 are required for BRCA2 (FANCD1) and SLX4 (FANCP) accumulation on the sex chromosomes during meiosis. In addition, FA proteins modulate distinct histone marks on the sex chromosomes: FA core proteins and FANCD2 regulate H3K9 methylation, while FANCD2 and RNF8 function together to regulate H3K4 methylation independently of FA core proteins...
October 18, 2016: Cell Reports
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