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https://www.readbyqxmd.com/read/28913972/significance-of-histone-methyltransferase-setdb1-expression-in-colon-adenocarcinoma
#1
Yi-Jung Ho, Yueh-Min Lin, Yen-Chi Huang, Jungshan Chang, Kun-Tu Yeh, Liang-In Lin, Zhiyuan Gong, Tsai-Yu Tzeng, Jeng-Wei Lu
This study investigated the clinical implications of SETDB1 (also known as KMT1E) in human colon adenocarcinoma. Expression levels of SETDB1 proteins were analyzed by immunohistochemistry staining, and tissue microarrays were used to examine expression profiles in human patients. Our results revealed that SETDB1 protein expression was significantly higher in tumor tissue than in normal tissue for the breast, colon, liver, and lung (p < 0.05). Moreover, an analysis with SurvExpress software suggested that elevated expression of SETDB1 mRNA was significantly associated with the overall survival of colon adenocarcinoma patients (p < 0...
September 15, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28903384/a-novel-sharpin-prmt5-h3r2me1-axis-is-essential-for-lung-cancer-cell-invasion
#2
Tingxiong Fu, Xiuwei Lv, Qingzhi Kong, Changjing Yuan
SHARPIN (Shank-associated RH domain interacting protein) is the main component of the linear ubiquitin chain activation complex (LUBAC). SHARPIN is involved in regulating inflammation and cancer progression. However, whether SHARPIN plays an important role in lung cancer metastasis and the potential underlying mechanism are still unknown. Here, for the first time, we reported that SHARPIN expression is closely related to lung cancer progression. Moreover, SHARPIN plays a central role in controlling lung cancer cell metastasis...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903350/zeb1-confers-stem-cell-like-properties-in-breast-cancer-by-targeting-neurogenin-3
#3
Chen Zhou, Huimin Jiang, Zhen Zhang, Guomin Zhang, Hang Wang, Quansheng Zhang, Peiqing Sun, Rong Xiang, Shuang Yang
Cancer stem cells (CSCs) are a subpopulation of cancer cells believed to be implicated in cancer initiation, progression, and recurrence. Here, we report that ectopic expression of zinc finger E-box binding homeobox 1 protein (ZEB1) results in the acquisition of CSC properties by breast cancer cells, leading to tumor initiation and progression in vitro and in vivo. The neurogenin 3 gene (Ngn3) is a bona fide target of ZEB1, and its repression is a key factor contributing to ZEB1-induced cancer cell stemness...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903048/set2-methyltransferase-facilitates-dna-replication-and-promotes-genotoxic-stress-responses-through-mbf-dependent-transcription
#4
Chen-Chun Pai, Anastasiya Kishkevich, Rachel S Deegan, Andrea Keszthelyi, Lisa Folkes, Stephen E Kearsey, Nagore De León, Ignacio Soriano, Robertus Antonius Maria de Bruin, Antony M Carr, Timothy C Humphrey
Chromatin modification through histone H3 lysine 36 methylation by the SETD2 tumor suppressor plays a key role in maintaining genome stability. Here, we describe a role for Set2-dependent H3K36 methylation in facilitating DNA replication and the transcriptional responses to both replication stress and DNA damage through promoting MluI cell-cycle box (MCB) binding factor (MBF)-complex-dependent transcription in fission yeast. Set2 loss leads to reduced MBF-dependent ribonucleotide reductase (RNR) expression, reduced deoxyribonucleoside triphosphate (dNTP) synthesis, altered replication origin firing, and a checkpoint-dependent S-phase delay...
September 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/28902362/histone-lysine-methylation-and-congenital-heart-disease-from-bench-to-bedside-review
#5
Xin Yi, Xuejun Jiang, Xiaoyan Li, Ding-Sheng Jiang
Histone post-translational modifications (PTM) as one of the key epigenetic regulatory mechanisms that plays critical role in various biological processes, including regulating chromatin structure dynamics and gene expression. Histone lysine methyltransferase contributes to the establishment and maintenance of differential histone methylation status, which can recognize histone methylated sites and build an association between these modifications and their downstream processes. Recently, it was found that abnormalities in the histone lysine methylation level or pattern may lead to the occurrence of many types of cardiovascular diseases, such as congenital heart disease (CHD)...
October 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28901481/silencing-of-histone-methyltransferase-nsd3-reduces-cell-viability-in-osteosarcoma-with-induction-of-apoptosis
#6
Zhiwei Liu, Lianhua Piao, Ming Zhuang, Xubin Qiu, Xiaoshuang Xu, Dawei Zhang, Mengmeng Liu, Ding Ren
NSD3 is a histone lysine methyltransferase that methylates histone H3 at lysine 36. NSD3 is located at chromosome 8p11.23, the locus that exhibits strong cancer relevance. Thus, NSD3 is likely involved in multiple human cancers. Nevertheless, its roles in human carcinogenesis remain unknown. In the present study, we demonstrated that silencing of NSD3 in osteosarcoma, the most common primary bone cancer in children and adolescents, results in a marked decrease in the number of viable cancer cells, accompanied by increases in the cell population at the G2/M phase and the number of apoptotic cells...
September 4, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28900200/differential-landscape-of-non-cpg-methylation-in-embryonic-stem-cells-and-neurons-caused-by-dnmt3s
#7
Jong-Hun Lee, Sung-Joon Park, Kenta Nakai
Methylated non-CpGs (mCpH; H means A, C, and T) have emerged as key epigenetic marks in mammalian embryonic stem cells (ESCs) and neurons, regulating cell type-specific functions. In these two cell types, mCpHs show distinct motifs and correlations to transcription that could be a key in understanding the cell type-specific regulations. Thus, we attempted to uncover the underlying mechanism of the differences in ESCs and neurons by conducting a comprehensive analysis of public whole genome bisulfite sequencing data...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28892470/different-molecular-complexes-that-mediate-transcriptional-induction-and-repression-by-foxp3
#8
Ho-Keun Kwon, Hui-Min Chen, Diane Mathis, Christophe Benoist
FoxP3 conditions the transcriptional signature and functional facets of regulatory T cells (Treg cells). Its mechanism of action, whether as an activator or a repressor, has remained unclear. Here, chromatin analysis showed that FoxP3 bound active enhancer elements, not repressed chromatin, around loci over- or under-expressed in Treg cells. We evaluated the impact of a panel of FoxP3 mutants on its transcriptional activity and interactions with DNA, transcriptional cofactors and chromatin. Computational integration, confirmed by biochemical interaction and size analyses, showed that FoxP3 existed in distinct multimolecular complexes...
September 11, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28890329/histone-methyltransferase-setdb1-maintains-survival-of-mouse-spermatogonial-stem-progenitor-cells-via-pten-akt-foxo1-pathway
#9
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/28889393/epigenetic-treatment-options-in-urothelial-carcinoma
#10
Maria Pinkerneil, Michèle J Hoffmann, Günter Niegisch
Mutations, dysregulation, and dysbalance of epigenetic regulators are especially frequent in urothelial carcinoma (UC) compared to other malignancies. Accordingly, targeting epigenetic regulators may provide a window of opportunity particularly in anticancer therapy of UC. In general, these epigenetic regulators comprise DNA methyltransferases and DNA demethylases (for DNA methylation), histone methyltransferases, and histone demethylases (for histone methylation) as well as acetyl transferases and histone deacetylases (for histone and non-histone acetylation)...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28887218/the-histone-lysine-methyltransferase-ezh2-is-required-for-maintenance-of-the-intestine-integrity-and-for-caudal-fin-regeneration-in-zebrafish
#11
Barbara Dupret, Pamela Völkel, Constance Vennin, Robert-Alain Toillon, Xuefen Le Bourhis, Pierre-Olivier Angrand
The histone lysine methyltransferase EZH2, as part of the Polycomb Repressive Complex 2 (PRC2), mediates H3K27me3 methylation which is involved in gene expression program repression. Through its action, EZH2 controls cell-fate decisions during the development and the differentiation processes. Here, we report the generation and the characterization of an ezh2-deficient zebrafish line. In contrast to its essential role in mouse early development, loss of ezh2 function does not affect zebrafish gastrulation. Ezh2 zebrafish mutants present a normal body plan but die at around 12 dpf with defects in the intestine wall, due to enhanced cell death...
September 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28882854/mutation-of-arabidopsis-smc4-identifies-condensin-as-a-corepressor-of-pericentromeric-transposons-and-conditionally-expressed-genes
#12
Jing Wang, Todd Blevins, Ram Podicheti, Jeremy R Haag, Ek Han Tan, Feng Wang, Craig S Pikaard
In eukaryotes, transcriptionally inactive loci are enriched within highly condensed heterochromatin. In plants, as in mammals, the DNA of heterochromatin is densely methylated and wrapped by histones displaying a characteristic subset of post-translational modifications. Growing evidence indicates that these chromatin modifications are not sufficient for silencing. Instead, they are prerequisites for further assembly of higher-order chromatin structures that are refractory to transcription but not fully understood...
September 7, 2017: Genes & Development
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
#13
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/28878842/efficacy-of-ezh2-inhibitory-drugs-in-human-papillomavirus-positive-and-human-papillomavirus-negative-oropharyngeal-squamous-cell-carcinomas
#14
Cameron D Lindsay, Morris A Kostiuk, Jeff Harris, Daniel A O'Connell, Hadi Seikaly, Vincent L Biron
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer worldwide with rates of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) dramatically increasing. The overexpression of enhancer of zeste homolog 2 (EZH2), a histone methyltransferase responsible for the trimethylation at lysine 27 of histone 3 (H3K27me3), is associated with a poor clinical prognosis and aggressive HPV-positive phenotypes. METHODS: We utilized three EZH2 pathway inhibitors, GSK-343, DZNeP, and EPZ-5687, and tested their efficacy in two HPV-positive and two HPV-negative OPSCC cell lines...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28874563/epigenetic-control-via-allosteric-regulation-of-mammalian-protein-arginine-methyltransferases
#15
Kanishk Jain, Cyrus Y Jin, Steven G Clarke
Arginine methylation on histones is a central player in epigenetics and in gene activation and repression. Protein arginine methyltransferase (PRMT) activity has been implicated in stem cell pluripotency, cancer metastasis, and tumorigenesis. The expression of one of the nine mammalian PRMTs, PRMT5, affects the levels of symmetric dimethylarginine (SDMA) at Arg-3 on histone H4, leading to the repression of genes which are related to disease progression in lymphoma and leukemia. Another PRMT, PRMT7, also affects SDMA levels at the same site despite its unique monomethylating activity and the lack of any evidence for PRMT7-catalyzed histone H4 Arg-3 methylation...
September 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28868353/dual-epigenetic-modifiers-for-cancer-therapy
#16
Edurne San José-Enériz, Obdulia Rabal, Xabier Agirre, Julen Oyarzabal, Felipe Prosper
Epigenetic drug discovery is an emerging strategy for the treatment of cancer and other pathologies. Here, we discuss our recent discovery of first-in-class dual reversible inhibitors of the histone methyltransferase activity of G9a/EHMT2 and DNA methyltransferases showing in vivo efficacy in human tumors. Current and future investigation lines are presented.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28864533/first-critical-repressive-h3k27me3-marks-in-embryonic-stem-cells-identified-using-designed-protein-inhibitor
#17
James D Moody, Shiri Levy, Julie Mathieu, Yalan Xing, Woojin Kim, Cheng Dong, Wolfram Tempel, Aaron M Robitaille, Luke T Dang, Amy Ferreccio, Damien Detraux, Sonia Sidhu, Licheng Zhu, Lauren Carter, Chao Xu, Cristina Valensisi, Yuliang Wang, R David Hawkins, Jinrong Min, Randall T Moon, Stuart H Orkin, David Baker, Hannele Ruohola-Baker
The polycomb repressive complex 2 (PRC2) histone methyltransferase plays a central role in epigenetic regulation in development and in cancer, and hence to interrogate its role in a specific developmental transition, methods are needed for disrupting function of the complex with high temporal and spatial precision. The catalytic and substrate recognition functions of PRC2 are coupled by binding of the N-terminal helix of the Ezh2 methylase to an extended groove on the EED trimethyl lysine binding subunit. Disrupting PRC2 function can in principle be achieved by blocking this single interaction, but there are few approaches for blocking specific protein-protein interactions in living cells and organisms...
September 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28863786/prdm13-forms-a-feedback-loop-with-ptf1a-and-is-required-for-glycinergic-amacrine-cell-genesis-in-the-xenopus-retina
#18
Nathalie Bessodes, Karine Parain, Odile Bronchain, Eric J Bellefroid, Muriel Perron
BACKGROUND: Amacrine interneurons that modulate synaptic plasticity between bipolar and ganglion cells constitute the most diverse cell type in the retina. Most are inhibitory neurons using either GABA or glycine as neurotransmitters. Although several transcription factors involved in amacrine cell fate determination have been identified, mechanisms underlying amacrine cell subtype specification remain to be further understood. The Prdm13 histone methyltransferase encoding gene is a target of the transcription factor Ptf1a, an essential regulator of inhibitory neuron cell fate in the retina...
September 1, 2017: Neural Development
https://www.readbyqxmd.com/read/28854561/sulforaphane-suppresses-prmt5-mep50-function-in-epidermal-squamous-cell-carcinoma-leading-to-reduced-tumor-formation
#19
Kamalika Saha, Matthew L Fisher, Gautam Adhikary, Daniel Grun, Richard L Eckert
Protein arginine methyltransferase 5 (PRMT5) cooperates with methylosome protein 50 (MEP50) to arginine methylate histone H3 and H4 to silence gene expression, and increased PRMT5 activity is associated with enhanced cancer cell survival. We have studied the role of PRMT5 and MEP50 in epidermal squamous cell carcinoma. We show that knockdown of PRMT5 or MEP50 results in reduced H4R3me2s formation, and reduced cell proliferation, invasion, migration and tumor formation. We further show that treatment with sulforaphane (SFN), a cancer preventive agent derived from cruciferous vegetables, reduces PRMT5 and MEP50 level and H4R3me2s formation, and this is associated with reduced cell proliferation, invasion and migration...
August 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28852907/functional-role-of-suv39h1-in-human-renal-tubular-epithelial-cells-under-high-glucose-ambiance
#20
Jiayi Wang, Wenzhe Yan, Xiaofei Peng, Yafeng Jiang, Liyu He, Youming Peng, Xian Chen, Muyao Ye, Hui Zhuo
SUV39H1, the histone methyltransferase (HMTase) of histone H3 lysine 9 trimethylation (H3K9me3), is a known transcriptional repressor of inflammatory genes. The effect of SUV39H1 on inflammatory gene promoters under high-glucose stimulation in vascular smooth muscle cells (VSMCs), macrophages, and cardiomyocytes has been studied, but how SUV39H1 functions in renal tubules under diabetic conditions is unclear. Renal biopsy specimens of ten diabetic nephropathy (DN) subjects and seven non-DN minimal change diseases (MCD) subjects were collected...
August 29, 2017: Inflammation
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