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https://www.readbyqxmd.com/read/29139562/lncrna-ghet1-predicts-poor-prognosis-in-hepatocellular-carcinoma-and-promotes-cell-proliferation-by-silencing-klf2
#1
Li Jin, Yangke He, Shijia Tang, Shan Huang
BACKGROUND: Hepatocellular carcinoma (HCC) has been identified as one of the leading causes of cancer-related death worldwide. Recently, long non-coding RNAs (lncRNAs) attract much attention of researchers, and they are demonstrated to be dysregulated in a variety of cancers, including HCC. LncRNA gastric carcinoma high expressed transcript 1 lncRNA GHET1 is found to be dysregulated in gastric cancer (GC). However, its clinical value and potential biological function in HCC remains unclear...
November 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29137925/polycomb-repression-complex-2-is-required-for-the-maintenance-of-retinal-progenitor-cells-and-balanced-retinal-differentiation
#2
Naoko Fujimura, Andrea Kuzelova, Anja Ebert, Hynek Strnad, Jitka Lachova, Ondrej Machon, Meinrad Busslinger, Zbynek Kozmik
Polycomb repressive complexes maintain transcriptional repression of genes encoding crucial developmental regulators through chromatin modification. Here we investigated the role of Polycomb repressive complex 2 (PRC2) in retinal development by inactivating its key components Eed and Ezh2. Conditional deletion of Ezh2 resulted in a partial loss of PRC2 function and accelerated differentiation of Müller glial cells. In contrast, inactivation of Eed led to the ablation of PRC2 function at early postnatal stage...
November 11, 2017: Developmental Biology
https://www.readbyqxmd.com/read/29118015/anril-regulates-production-of-extracellular-matrix-proteins-and-vasoactive-factors-in-diabetic-complications
#3
Anu Alice Thomas, Biao Feng, Subrata Chakrabarti
Long non-coding RNAs (lncRNAs) have gained widespread interest due to their prevailing presence in various diseases. lncRNA ANRIL (a.k.a CDKN2B-AS1) is located on human chromosome 9 (p21.3) and transcribed in opposite direction to INK4b-ARF-INK4a gene cluster. It has been identified as highly susceptible region for diseases such as coronary artery diseases and Type 2 Diabetes. Here we explored its regulatory role in diabetic nephropathy (DN) and diabetic cardiomyopathy (DCM) in association with epigenetic modifiers p300 and polycomb repressive complex 2 (PRC2) complex...
November 7, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29113297/long-non-coding-rna-profile-in-mantle-cell-lymphoma-identifies-a-functional-lncrna-ror1-as1-associated-with-ezh2-prc2-complex
#4
Guangzhen Hu, Shiv K Gupta, Tammy P Troska, Asha Nair, Mamta Gupta
Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by rapid disease progression. The needs for new therapeutic strategies for MCL patients call for further understanding on the molecular mechanisms of pathogenesis of MCL. Recently, long noncoding RNAs (lncRNAs) have been recognized as key regulators of gene expression and disease development, however, the role of lncRNAs in non-Hodgkin lymphoma and specifically in MCL is still unknown. Next generation RNA-sequencing was carried out on MCL patient samples along with normal controls and data was analyzed...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29111977/nanos-promotes-epigenetic-reprograming-of-the-germline-by-down-regulation-of-the-thap-transcription-factor-lin-15b
#5
Chih-Yung Sean Lee, Tu Lu, Geraldine Seydoux
Nanos RNA-binding proteins are required for germline development in metazoans, but the underlying mechanisms remain poorly understood. We have profiled the transcriptome of primordial germ cells (PGCs) lacking the nanos homologs nos-1 and nos-2 in C. elegans. nos-1nos-2 PGCs fail to silence hundreds of transcripts normally expressed in oocytes. We find that this misregulation is due to both delayed turnover of maternal transcripts and inappropriate transcriptional activation. The latter appears to be an indirect consequence of delayed turnover of the maternally-inherited transcription factor LIN-15B, a synMuvB class transcription factor known to antagonize PRC2 activity...
November 7, 2017: ELife
https://www.readbyqxmd.com/read/29106391/aberrant-gata2-epigenetic-dysregulation-induces-a-gata2-gata6-switch-in-human-gastric-cancer
#6
S H Song, M S Jeon, J W Nam, J K Kang, Y J Lee, J Y Kang, H P Kim, S W Han, G H Kang, T Y Kim
Six GATA transcription factors play important roles in eukaryotic development. Among these, GATA2, an essential factor for the hematopoietic cell lineage, exhibits low expression in human gastric tissues, whereas GATA6, which is crucial for gastrointestinal development and differentiation, is frequently amplified and/or overexpressed in human gastric cancer. Interestingly, we found that GATA6 was overexpressed in human gastric cancer cells only when GATA2 expression was completely absent, thereby showing an inverse correlation between GATA2 and GATA6...
November 6, 2017: Oncogene
https://www.readbyqxmd.com/read/29102770/overexpression-of-djmj-differentially-affects-intestinal-stem-cells-and-differentiated-enterocytes
#7
Dang Ngoc Anh Suong, Kouhei Shimaji, Jung-Hoon Pyo, Joung-Sun Park, Hideki Yoshida, Mi-Ae Yoo, Masamitsu Yamaguchi
Jumonji (Jmj)/Jarid2 is a DNA-binding transcriptional repressor mediated via histone methylation. Nevertheless, the well-known function of Jmj is as a scaffold for the recruitment of various complexes including Polycomb repressive complex 2 (PRC2), and required for mouse embryonic stem cell development. However, PRC2 independent function is suggested for Drosophila Jumonji (dJmj). To clarify the function of dJmj during cell differentiation, we used Drosophila adult intestinal stem cell system that allows to follow stem cell behaviors in vivo...
November 2, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29100324/modulation-of-the-fanconi-anemia-pathway-via-chemically-induced-changes-in-chromatin-structure
#8
David A Vierra, Jada L Garzon, Meghan A Rego, Morganne M Adroved, Maurizio Mauro, Niall G Howlett
Fanconi anemia (FA) is a rare disease characterized by congenital defects, bone marrow failure, and atypically early-onset cancers. The FA proteins function cooperatively to repair DNA interstrand crosslinks. A major step in the activation of the pathway is the monoubiquitination of the FANCD2 and FANCI proteins, and their recruitment to chromatin-associated nuclear foci. The regulation and function of FANCD2 and FANCI, however, is poorly understood. In addition, how chromatin state impacts pathway activation is also unknown...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29091973/dynamic-regulation-of-ezh2-from-hpsc-to-hepatocyte-like-cell-fate
#9
Mariaelena Pistoni, Nicky Helsen, Jolien Vanhove, Ruben Boon, Zhuofei Xu, Laura Ordovas, Catherine M Verfaillie
Currently, drug metabolization and toxicity studies rely on the use of primary human hepatocytes and hepatoma cell lines, which both have conceivable limitations. Human pluripotent stem cell (hPSC)-derived hepatocyte-like cells (HLCs) are an alternative and valuable source of hepatocytes that can overcome these limitations. EZH2 (enhancer of zeste homolog 2), a transcriptional repressor of the polycomb repressive complex 2 (PRC2), may play an important role in hepatocyte development, but its role during in vitro hPSC-HLC differentiation has not yet been assessed...
2017: PloS One
https://www.readbyqxmd.com/read/29078818/the-human-lncrna-linc-pint-inhibits-tumor-cell-invasion-through-a-highly-conserved-sequence-element
#10
Oskar Marín-Béjar, Aina M Mas, Jovanna González, Dannys Martinez, Alejandro Athie, Xabier Morales, Mikel Galduroz, Ivan Raimondi, Elena Grossi, Shuling Guo, Ana Rouzaut, Igor Ulitsky, Maite Huarte
BACKGROUND: It is now obvious that the majority of cellular transcripts do not code for proteins, and a significant subset of them are long non-coding RNAs (lncRNAs). Many lncRNAs show aberrant expression in cancer, and some of them have been linked to cell transformation. However, the underlying mechanisms remain poorly understood and it is unknown how the sequences of lncRNA dictate their function. RESULTS: Here we characterize the function of the p53-regulated human lncRNA LINC-PINT in cancer...
October 27, 2017: Genome Biology
https://www.readbyqxmd.com/read/29074395/epigenetics-of-malignant-melanoma
#11
REVIEW
Bruce Moran, Romina Silva, Antoinette S Perry, William M Gallagher
Patients with malignant melanoma generally have a good prognosis if the disease presents prior to metastasis. Due to progress with targeted and immunotherapies, the median survival of metastatic melanoma patients is now over 2 years. The disease is characterised by one of the highest somatic mutation rates observed amongst cancer types, with a specific mutational signature based on UV radiation damage evident. Highly prevalent mutations, such as the BRAF(V600E), in the MAPK cascade indicate truncal involvement of this pathway in the earliest stage of melanoma...
October 23, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29059780/re-loss-of-tumor-suppressor-kdm6a-amplifies-prc2-regulated-transcriptional-repression-in-bladder-cancer-and-can-be-targeted-through-inhibition-of-ezh2
#12
https://www.readbyqxmd.com/read/29058710/dna-binding-by-phf1-prolongs-prc2-residence-time-on-chromatin-and-thereby-promotes-h3k27-methylation
#13
Jeongyoon Choi, Andreas Linus Bachmann, Katharina Tauscher, Christian Benda, Beat Fierz, Jürg Müller
Polycomb repressive complex 2 (PRC2) trimethylates histone H3 at lysine 27 to mark genes for repression. We measured the dynamics of PRC2 binding on recombinant chromatin and free DNA at the single-molecule level using total internal reflection fluorescence (TIRF) microscopy. PRC2 preferentially binds free DNA with multisecond residence time and midnanomolar affinity. PHF1, a PRC2 accessory protein of the Polycomblike family, extends PRC2 residence time on DNA and chromatin. Crystallographic and functional studies reveal that Polycomblike proteins contain a winged-helix domain that binds DNA in a sequence-nonspecific fashion...
October 23, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/29058709/molecular-analysis-of-prc2-recruitment-to-dna-in-chromatin-and-its-inhibition-by-rna
#14
Xueyin Wang, Richard D Paucek, Anne R Gooding, Zachary Z Brown, Eva J Ge, Tom W Muir, Thomas R Cech
Many studies have revealed pathways of epigenetic gene silencing by Polycomb repressive complex 2 (PRC2) in vivo, but understanding the underlying molecular mechanisms requires biochemistry. Here we analyze interactions of reconstituted human PRC2 with nucleosome complexes. Histone modifications, the H3K27M cancer mutation, and inclusion of JARID2 or EZH1 in the PRC2 complex have unexpectedly minor effects on PRC2-nucleosome binding. Instead, protein-free linker DNA dominates the PRC2-nucleosome interaction...
October 23, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/29048549/curcumin-sensitizes-pancreatic-cancer-cells-to-gemcitabine-by-attenuating-prc2-subunit-ezh2-and-the-lncrna-pvt1-expression
#15
Kazuhiro Yoshida, Shusuke Toden, Preethi Ravindranathan, Haiyong Han, Ajay Goel
Development of resistance to chemotherapeutic drugs is a major challenge in the care of patients with pancreatic ductal adenocarcinoma (PDAC). Acquired resistance to chemotherapeutic agents in PDAC has been linked to a subset of cancer cells termed 'cancer stem cells' (CSCs). Therefore, an improved understanding of the molecular events underlying the development of pancreatic CSCs is required to identify new therapeutic targets to overcome chemoresistance. Accumulating evidence indicates that curcumin, a phenolic compound extracted from turmeric, can overcome de novo chemoresistance and re-sensitize tumors to various chemotherapeutic agents...
October 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29033324/the-elongation-factor-spt6-maintains-esc-pluripotency-by-controlling-super-enhancers-and-counteracting-polycomb-proteins
#16
A Hongjun Wang, Aster H Juan, Kyung Dae Ko, Pei-Fang Tsai, Hossein Zare, Stefania Dell'Orso, Vittorio Sartorelli
Spt6 coordinates nucleosome dis- and re-assembly, transcriptional elongation, and mRNA processing. Here, we report that depleting Spt6 in embryonic stem cells (ESCs) reduced expression of pluripotency factors, increased expression of cell-lineage-affiliated developmental regulators, and induced cell morphological and biochemical changes indicative of ESC differentiation. Selective downregulation of pluripotency factors upon Spt6 depletion may be mechanistically explained by its enrichment at ESC super-enhancers, where Spt6 controls histone H3K27 acetylation and methylation and super-enhancer RNA transcription...
October 19, 2017: Molecular Cell
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
#17
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/28992244/lincrna-1614-coordinates-sox2-prc2-mediated-repression-of-developmental-genes-in-pluripotency-maintenance
#18
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/28984200/incorporating-genomic-transcriptomic-and-clinical-data-a-prognostic-and-stem-cell-like-myc-and-prc-imbalance-in-high-risk-neuroblastoma
#19
Xinan Holly Yang, Fangming Tang, Jisu Shin, John M Cunningham
BACKGROUND: Previous studies suggested that cancer cells possess traits reminiscent of the biological mechanisms ascribed to normal embryonic stem cells (ESCs) regulated by MYC and Polycomb repressive complex 2 (PRC2). Several poorly differentiated adult tumors showed preferentially high expression levels in targets of MYC, coincident with low expression levels in targets of PRC2. This paper will reveal this ESC-like cancer signature in high-risk neuroblastoma (HR-NB), the most common extracranial solid tumor in children...
October 3, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28955347/blister-regulates-polycomb-target-genes-represses-stress-regulated-genes-and-promotes-stress-responses-in-arabidopsis-thaliana
#20
Julia A Kleinmanns, Nicole Schatlowski, David Heckmann, Daniel Schubert
HIGHLIGHTS The PRC2 interacting protein BLISTER likely acts downstream of PRC2 to silence Polycomb target genes and is a key regulator of specific stress responses in Arabidopsis. Polycomb group (PcG) proteins are key epigenetic regulators of development. The highly conserved Polycomb repressive complex 2 (PRC2) represses thousands of target genes by trimethylating H3K27 (H3K27me3). Plant specific PcG components and functions are largely unknown, however, we previously identified the plant-specific protein BLISTER (BLI) as a PRC2 interactor...
2017: Frontiers in Plant Science
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