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https://www.readbyqxmd.com/read/29028630/ezh2-regulates-dental-pulp-inflammation-by-direct-effect-on-inflammatory-factors
#1
Tianqian Hui, Peng A, Yuan Zhao, Jing Yang, Ling Ye, Chenglin Wang
OBJECTIVE: Pulpitis is a multi-factorial disease that could be caused by complex interactions between genetics, epigenetics and environmental factors. We aimed to evaluate the role of Enhancer of Zeste Homolog 2 (EZH2) in the inflammatory response of human dental pulp cells (HDPCs) and dental pulp tissues. METHODS: The expressions of inflammatory cytokines in HDPCs treated by EZH2 complex or EZH2 siRNA with or without rhTNF-α were examined by quantitative real-time polymerase chain reaction (q-PCR)...
October 7, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/29026152/genetic-and-epigenetic-profiling-reveals-ezh2-mediated-down-regulation-of-oct-4-involves-nr2f2-during-cardiac-differentiation-of-human-embryonic-stem-cells
#2
Varsha Pursani, Prasad Pethe, Mohsin Bashir, Prabha Sampath, Vivek Tanavde, Deepa Bhartiya
Human embryonic (hES) stem cells are widely used as an in vitro model to understand global genetic and epigenetic changes that occur during early embryonic development. In-house derived hES cells (KIND1) were subjected to directed differentiation into cardiovascular progenitors (D12) and beating cardiomyocytes (D20). Transcriptome profiling of undifferentiated (D0) and differentiated (D12 and 20) cells was undertaken by microarray analysis. ChIP and sequential ChIP were employed to study role of transcription factor NR2F2 during hES cells differentiation...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29026085/ezh2-enables-germinal-centre-formation-through-epigenetic-silencing-of-cdkn1a-and-an-rb-e2f1-feedback-loop
#3
Wendy Béguelin, Martín A Rivas, María T Calvo Fernández, Matt Teater, Alberto Purwada, David Redmond, Hao Shen, Matt F Challman, Olivier Elemento, Ankur Singh, Ari M Melnick
The EZH2 histone methyltransferase is required for B cells to form germinal centers (GC). Here we show that EZH2 mediates GC formation through repression of cyclin-dependent kinase inhibitor CDKN1A (p21(Cip1)). Deletion of Cdkn1a rescues the GC reaction in Ezh2 (-/-) mice. Using a 3D B cell follicular organoid system that mimics the GC reaction, we show that depletion of EZH2 suppresses G1 to S phase transition of GC B cells in a Cdkn1a-dependent manner. GC B cells of Cdkn1a (-/-) Ezh2 (-/-) mice have high levels of phospho-Rb, indicating that loss of Cdkn1a enables progression of cell cycle...
October 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/29024646/the-epstein-barr-virus-regulome-in-lymphoblastoid-cells
#4
Sizun Jiang, Hufeng Zhou, Jun Liang, Catherine Gerdt, Chong Wang, Liangru Ke, Stefanie C S Schmidt, Yohei Narita, Yijie Ma, Shuangqi Wang, Tyler Colson, Benjamin Gewurz, Guoliang Li, Elliott Kieff, Bo Zhao
Epstein-Barr virus (EBV) transforms B cells to continuously proliferating lymphoblastoid cell lines (LCLs), which represent an experimental model for EBV-associated cancers. EBV nuclear antigens (EBNAs) and LMP1 are EBV transcriptional regulators that are essential for LCL establishment, proliferation, and survival. Starting with the 3D genome organization map of LCL, we constructed a comprehensive EBV regulome encompassing 1,992 viral/cellular genes and enhancers. Approximately 30% of genes essential for LCL growth were linked to EBV enhancers...
October 11, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/29024026/computational-characterization-of-substrate-and-product-specificities-and-functionality-of-sam-binding-pocket-in-histone-lysine-methyltransferases-from-arabidopsis-rice-and-maize
#5
Mutyala Satish, M Angel Nivya, Suman Abhishek, Naveen Kumar Nakarakanti, Dixit Shivani, M Vinuthna Vani, Eerappa Rajakumara
Histone lysine methylation by histone lysine methyltransferases (HKMTs) has been implicated in regulation of gene expression. While significant progress has been made to understand the roles and mechanisms of animal HKMT functions, only a few plant HKMTs are functionally characterized. To unravel histone substrate specificity, degree of methylation and catalytic activity, we analysed ATX, SUVH, SUVR, ATXR5, ATXR6, and E(Z) HKMTs of Arabidopsis, maize and rice through sequence and structure comparison. We show that ATXs may exhibit methyltransferase specificity towards histone 3 lysine 4 (H3K4) and might catalyse the tri-methylation...
October 11, 2017: Proteins
https://www.readbyqxmd.com/read/29022920/the-lncrna-tug1-modulates-proliferation-in-trophoblast-cells-via-epigenetic-suppression-of-rnd3
#6
Yetao Xu, Zhiping Ge, Erbao Zhang, Qing Zuo, Shiyun Huang, Nana Yang, Dan Wu, Yuanyuan Zhang, Yanzi Chen, Haoqin Xu, Huan Huang, Zhiyan Jiang, Lizhou Sun
Due to limited treatment options, pre-eclampsia (PE) is associated with fetal perinatal and maternal morbidity and mortality. During the causes of PE, failure of uterine spiral artery remodeling which might be related to functioning abnormally of trophoblast cells, result in the occurrence and progression of PE. Recently, abnormal expression of long non-coding RNAs (lncRNAs), as imperative regulators involved in human diseases progression (included PE), which has been indicated by increasing evidence. In this research, we found that TUG1, a lncRNA, was markedly reduced in placental samples from patients with PE...
October 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29022893/mycn-contributes-to-the-malignant-characteristics-of-erythroleukemia-through-ezh2-mediated-epigenetic-repression-of-p21
#7
Li Liu, Feng Xu, Chun-Kang Chang, Qi He, Ling-Yun Wu, Zheng Zhang, Xiao Li
MYC proto-oncogene family including c-myc and n-myc (MYCN) are critical for normal cell development and tumorigenesis. Overexpression of c-myc causes acute erythroleukemia in vivo. However, the role of MYCN in acute erythroleukemia remains poorly understood. In this study, we found that the patients with erythroleukemia showed higher expression of MYCN than normal controls. In vitro experiments, knockdown of MYCN resulted in decreased cell proliferation, elevated autonomously cell apoptosis and increased P21-mediated cell senescence...
October 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29021137/ddb2-is-a-novel-regulator-of-wnt-signaling-in-colon-cancer
#8
Shuo Huang, Damiano Fantini, Brad Merrill, Srilata Bagchi, Grace Guzman, Pradip Raychaudhuri
Deregulation of the Wnt/β-catenin signaling pathway drives the development of colorectal cancer (CRC) but understanding of this pathway remains incomplete. Here we report that the damage-specific DNA-binding protein DDB2 is critical for β-catenin-mediated activation of RNF43, which restricts Wnt signaling by removing Wnt receptors from the cell surface. Reduced expression of DDB2 and RNF43 was observed in human hyperplastic colonic foci. DDB2 recruited EZH2 and β-catenin at an upstream site in the RNF43 gene, enabling functional interaction with distant TCF4/β-catenin binding sites in the intron of RNF43...
October 11, 2017: Cancer Research
https://www.readbyqxmd.com/read/28993276/a-distinctive-subgroup-of-oral-ebv-b-cell-neoplasm-with-polymorphous-features-is-potentially-identical-to-ebv-mucocutaneous-ulcer
#9
Yae Ohata, Anna Tatsuzawa, Yoshio Ohyama, Ayako Ichikawa, Yumi Mochizuki, Sachiko Ishibashi, Yuri Itakura, Kei Sakamoto, Tohru Ikeda, Masanobu Kitagawa, Kouhei Yamamoto
EBV-positive mucocutaneous ulcer (EBVMCU) is a newly recognized provisional entity, included in mature B-cell neoplasm in the latest 2016 World Health Organization Classification. It has a self-limited growth potential with a high predilection for oral cavities, and occurs in age-related or iatrogenic immunodeficiency with indolent clinical courses. However, it shares histological features with EBV-positive diffuse large B-cell lymphoma (DLBCL), and this often leads to diagnostic challenges and controversies in patients with an oral EBV-positive B-cell neoplasm...
October 6, 2017: Human Pathology
https://www.readbyqxmd.com/read/28992292/macroh2a1-1-cooperates-with-ezh2-to-promote-adipogenesis-by-regulating-wnt-signaling
#10
Danyang Wan, Chengyu Liu, Y Sun, Wenjun Wang, Kun Huang, Ling Zheng
White adipocytes play important roles in many physiological processes, including energy storage, endocrine signaling, and inflammatory responses. Understanding the molecular mechanisms of adipocyte formation (adipogenesis) provides insights into therapeutic approaches against obesity and its related diseases. Many transcriptional factors and epigenetic enzymes are known to regulate adipogenesis; however, whether histone variants play a role in this process is unknown. Here we found that macroH2A1.1 (mH2A1.1), a variant of histone H2A, was upregulated during adipocyte differentiation in 3T3-L1 cells and in the white adipose tissue of obese mice...
August 1, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/28992244/lincrna-1614-coordinates-sox2-prc2-mediated-repression-of-developmental-genes-in-pluripotency-maintenance
#11
Xudong Guo, Zikang Wang, Chenqi Lu, Wujun Hong, Guiying Wang, Yanxin Xu, Zhongmin Liu, Jiuhong Kang
Large-intergenic noncoding RNAs (lincRNAs) cooperate with core transcription factors to coordinate the pluripotency network of embryonic stem cells. The mechanisms by which lincRNAs affect chromatin structure and gene transcription remain mostly unknown. Here, we identified that a lincRNA (linc1614), occupied by pluripotency factors at its promoter, was indispensable for both maintenance and acquisition of pluripotency. Linc1614 served as a specific partner of core factor Sox2 in maintaining pluripotency, primarily by mediating the function of Sox2 in the repression of developmental genes...
September 14, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/28982932/ezh2-deletion-promotes-spermatogonial-differentiation-and-apoptosis
#12
Cheng Jin, Yan Zhang, Zhi-Peng Wang, Xiu-Xia Wang, Tie-Cheng Sun, Xiao-Yu Li, Ji-Xin Tang, Jin-Mei Cheng, Jian Li, Su-Ren Chen, Shou-Long Deng, Yi-Xun Liu
Spermatogenesis is crucial for male fertility and is therefore tightly controlled by a variety of epigenetic regulators. However, the function of enhancer of zeste homolog 2 (EZH2) in spermatogenesis and the molecular mechanisms underlying its activity remain poorly defined. Here, we demonstrate that deleting EZH2 promoted spermatogonial differentiation and apoptosis. EZH2 is expressed in spermatogonia, spermatocytes and round and elongated spermatids from stage 9 to 11 but not in leptotene and zygotene spermatocytes...
November 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28981099/long-non-coding-rna-snhg20-promotes-non-small-cell-lung-cancer-cell-proliferation-and-migration-by-epigenetically-silencing-of-p21-expression
#13
Zhenyao Chen, Xin Chen, Ping Chen, Shanxun Yu, Fengqi Nie, Binbin Lu, Te Zhang, Yue Zhou, Qinnan Chen, Chenchen Wei, Wei Wang, Zhaoxia Wang
Mounting evidence demonstrates that long non-coding RNAs (lncRNAs) are novel transcripts governing multiple biological processes, and their dysregulation is involved in the development and progression of multiple types of cancers. Small Nucleolar RNA Host Gene 20 (SNHG20) is a 2183 bp lncRNA, and its overexpression predicts poor prognosis in colorectal cancer and hepatocellular carcinoma. However, the clinical relevance of SNHG20 and its molecular mechanisms affecting cancer cell phenotype have not been documented...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28979810/enhancing-chemotherapy-sensitivity-by-targeting-pcg-via-the-atm-p53-pathway
#14
Shu-Bin Gao, Kang-Li Li, Huan Qiu, Ling-Yu Zhu, Chang-Bao Pan, Yue Zhao, Shu-Hua Wei, Shu Shi, Guang-Hui Jin, Li-Xiang Xue
Histone modification and chromatin remodeling are important events in response to DNA damage, and Polycomb group (PcG) proteins, catalyzing H3K27 methylation, are involved. However, the biological function and mechanism of PcG in DNA damage are not fully understood. Additionally, downstream effectors in hepatocellular carcinoma (HCC) remain unclear. The present study investigated the biological and mechanistic roles of PcG in the DNA damage response induced by chemotherapeutic drugs in HCC. It was found that chemotherapy drugs, such as epirubicin (EPB) and mitomycin C (MMC), effectively blocked expression of PcG in p53-wild-type HepG2 cells but not in PLC/PRF5 and Hep3B cells with p53 mutation or deletion...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28978842/molecular-pathogenesis-and-its-therapeutic-implication-for-atl
#15
Kenji Ishitsuka
Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-lymphotropic virus type I (HTLV-1). HTLV-1 related proteins Tax and HTLV-1 bZIP factor induce immortalization and transformation of HTLV-1-infected T-lymphocytes and eventually induce clonal proliferation. One of the apparent molecular features in ATL cells is abundant genomic abnormalities targeting characteristic pathways, including T-cell receptor signaling and the NF-κB pathway, G-protein coupled-receptor, including CCR4, and transcriptional regulation...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28978819/epigenetic-dysregulation-in-myelodysplastic-syndromes
#16
Goro Sashida
Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disease characterized by impaired hematopoiesis and an increased risk of transformation to acute myeloid leukemia (AML). Epigenetic regulators, including TET2, DNMT3A and EZH2, are often mutated in patients with MDS. Recently, exome sequencing of blood cells from aged people without hematological malignancies have demonstrated the presence of clonal hematopoiesis with myeloid malignancies-associated mutations, such as TET2 and DNMT3A. Here, I will discuss the molecular mechanisms underlying the accumulation of epigenetic alterations and genetic mutations, including TET2, DNMT3A and EZH2, and how these promote the development of MDS and hematological malignancies in aged people with clonal hematopoiesis...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28978636/ezh2-modifies-sunitinib-resistance-in-renal-cell-carcinoma-by-kinome-reprogramming
#17
Remi Adelaiye-Ogala, Justin Budka, Nur P Damayanti, Justine Arrington, Mary W Ferris, Chuan-Chih Hsu, Sreenivasulu Chintala, Ashley R Orillion, Kiersten Marie Miles, Li Shen, May Elbanna, Eric Ciamporcero, Sreevani Arisa, Piergiorgio Pettazzoni, Giulio F Draetta, Mukund Seshadri, Bradley A Hancock, Milan Radovich, Janaiah Kota, Michael Buck, Heike Keilhack, Brian P McCarthy, Scott A Persohn, Paul R Territo, Yong Zang, Joseph Irudayaraj, Andy W Tao, Peter Hollenhorst, Roberto Pili
Acquired and intrinsic resistance to receptor tyrosine kinase inhibitors (RTKi) represent a major hurdle in improving the management of clear cell renal cell carcinoma (ccRCC). Recent reports suggest that drug resistance is driven by tumor adaptation via epigenetic mechanisms that activate alternative survival pathways. The histone methyl transferase EZH2 is frequently altered in many cancers including ccRCC. To evaluate its role in ccRCC resistance to RTKi, we established and characterized a spontaneously metastatic, patient-derived xenograft (PDX) model that is intrinsically resistant to the RTKI sunitinib but not to the VEGF therapeutic antibody bevacizumab...
October 4, 2017: Cancer Research
https://www.readbyqxmd.com/read/28978137/the-histone-methyltransferase-ezh2-as-a-druggable-target-in-shh-medulloblastoma-cancer-stem-cells
#18
Evelina Miele, Sergio Valente, Vincenzo Alfano, Marianna Silvano, Paolo Mellini, Diana Borovika, Biagina Marrocco, Agnese Po, Zein Mersini Besharat, Giuseppina Catanzaro, Giuseppe Battaglia, Luana Abballe, Clemens Zwergel, Giulia Stazi, Ciro Milite, Sabrina Castellano, Marco Tafani, Peteris Trapencieris, Antonello Mai, Elisabetta Ferretti
The histone methyltransferase EZH2 plays a role in maintenance of the stem component of cancer, and its overexpression and/or mutation typically drives tumor aggressiveness, drug resistance and patients' poor prognosis. In this study, we use mouse and human medulloblastoma stem-like cells belonging to the Sonic Hedgehog subgroup (SHH MB-SLCs) and demonstrate that genetic suppression of EZH2 reduces the level of its histone mark H3K27me3 and lowers proliferation and self-renewal. We designed an EZH2 inhibitor (EZH2i) as a simplified analog of EPZ005687 and GSK2816126, MC3629, and we tested its biological activity in SHH MB-SLCs...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28978010/the-network-of-dab2ip-mir-138-in-regulating-drug-resistance-of-renal-cell-carcinoma-associated-with-stem-like-phenotypes
#19
Eun-Jin Yun, Jiancheng Zhou, Chun-Jung Lin, Shan Xu, John Santoyo, Elizabeth Hernandez, Chih-Ho Lai, Ho Lin, Dalin He, Jer-Tsong Hsieh
Targeted therapy is a standard of care for metastatic renal cell carcinoma (RCC) but the response rate is not overwhelmed, which only prolongs a short survival of patients due to the onset of therapeutic resistance. Although the mechanisms are not fully understood, the presence of cancer initiating cells (CIC) may underlie the drug resistance. Nevertheless, identifying CIC phenotypes with its biomarkers in RCC appear to be diverse and controversial from many reports. In this study, we took a different approach to focus on the regulatory mechanism in RCC-CIC and unveil DAB2IP-mediated miR-138 expression that plays a critical role in modulating stem-like phenotypes in RCC via targeting the ABC transporter (ABCA13) as well as oncogenic histone methyltransferase EZH2 while down regulation of miR-138 gene expression in RCC is due to epigenetic gene silencing by DNA methyltransferase 1 (DNMT1)...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977898/decreased-expression-of-mt1e-is-a-potential-biomarker-of-prostate-cancer-progression
#20
Rita Demidenko, Kristina Daniunaite, Arnas Bakavicius, Rasa Sabaliauskaite, Aiste Skeberdyte, Donatas Petroska, Arvydas Laurinavicius, Feliksas Jankevicius, Juozas R Lazutka, Sonata Jarmalaite
Differentiation of indolent and aggressive prostate carcinoma (PCa) at the time of diagnosis is currently one of the major challenges. This study aimed at identification of prognostic biomarkers to aid in predicting biochemical recurrence (BCR) of the disease. Microarray-based gene expression profiling in tissues of 8 BCR and 8 No-BCR cases revealed expression differences of 455 genes, most of which were down-regulated in BCR cases. Eleven genes were selected for validation by real-time PCR in the first PCa cohort (N = 55), while seven of them were further validated in the second, independent, PCa cohort (N = 53)...
September 22, 2017: Oncotarget
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