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polycomb repressor complex

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https://www.readbyqxmd.com/read/28423699/long-non-coding-rna-lucat1-is-associated-with-poor-prognosis-in-human-non-small-lung-cancer-and-regulates-cell-proliferation-via-epigenetically-repressing-p21-and-p57-expression
#1
Yue Sun, Shi-Dai Jin, Quan Zhu, Liang Han, Jing Feng, Xi-Yi Lu, Wei Wang, Feng Wang, Ren-Hua Guo
Recently, long non-coding RNAs (lncRNAs) have been recognized as playing key roles in regulating cellular processes, such as proliferation, invasion, and metastasis. These lncRNAs have been shown to be abnormally expressed in tumorigenic processes. However, the role and clinical relevance of LUCAT1 in non-small-cell lung cancer (NSCLC) remain unclear. In this study, we found that the expression of LUCAT1 was significantly up-regulated in NSCLC tissues compared to non-tumor tissues, and its expression was associated with tumor size, tumor-node-metastasis (TNM) stage and overall survival (OS)...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416772/dna-methylation-of-mettl7a-gene-body-regulates-its-transcriptional-level-in-thyroid-cancer
#2
Shasha Zhou, Yihang Shen, Min Zheng, Linlin Wang, Raymond Che, Wanning Hu, Pin Li
DNA methylation is the best-studied epigenetic mechanism for regulating gene transcription and maintaining genome stability. Current research progress of transcriptional regulation by DNA methylation mostly focuses on promoter region where hypomethylated CpG islands are present transcriptional activity, as hypermethylated CpG islands generally result in gene repression. Recently, the DNA methylation patterns across the gene body (intragenic methylation) have increasingly attracted attention towards their role in transcriptional regulation and efficiency, due to the improvement of numerous genome-wide DNA methylation profiling studies...
March 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415635/role-of-ezh2-in-cancer-stem-cells-from-biological-insight-to-a-therapeutic-target
#3
REVIEW
Yiping Wen, Jing Cai, Yaya Hou, Zaiju Huang, Zehua Wang
Epigenetic modifications in cancer stem cells largely result in phenotypic and functional heterogeneity in many solid tumors. Increasing evidence indicates that enhancer of zeste homolog 2 (EZH2), the catalytic subunit of Polycomb repressor complex 2, is highly expressed in cancer stem cells of numerous malignant tumors and has a critical function in cancer stem cell expansion and maintenance. Here, we review up-to-date information regarding EZH2 expression patterns, functions, and molecular mechanisms in cancer stem cells in various malignant tumors and discuss the therapeutic potential of targeting EZH2 in tumors...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410242/functional-and-therapeutic-significance-of-ezh2-in-urological-cancers
#4
Xiaobing Liu, Qingjian Wu, Longkun Li
The enhancer of zeste homolog 2 (EZH2) is a core subunit of the polycomb repressor complex 2 (PRC2), which is overexpressed in numerous cancers and mutated in several others. Notably, EZH2 acts not only a critical epigenetic repressor through its role in histone methylation, it is also an activator of gene expression, acting through multiple signaling pathways in distinct cancer types. Increasing evidence suggests that EZH2 is an oncogene and is central to initiation, growth and progression of urological cancers...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28359242/small-molecule-inhibitors-of-epigenetic-mutations-as-compelling-drug-targets-for-myelodysplastic-syndromes
#5
Bani Bandana Ganguly
BACKGROUND: Involvement of mutations in epigenetic mechanism in development of heterogeneous MDS and its evolution to AML has been understood with at least one mutation and median of 2-3 mutations of the landscapes of driver mutations in ~40 genes described >90% MDS patients. Exclusivity and cooperating effects of mutations have directed therapeutic implementation with hypomethylating agents and identified a number of first-in-class small molecules as inhibitors of mutational expression...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28340355/the-human-immunodeficiency-virus-1-asp-rna-promotes-viral-latency-by-recruiting-the-polycomb-repressor-complex-2-and-promoting-nucleosome-assembly
#6
Juan C Zapata, Federica Campilongo, Robert A Barclay, Catherine DeMarino, Maria D Iglesias-Ussel, Fatah Kashanchi, Fabio Romerio
Various epigenetic marks at the HIV-1 5'LTR suppress proviral expression and promote latency. Cellular antisense transcripts known as long noncoding RNAs (lncRNAs) recruit the polycomb repressor complex 2 (PRC2) to gene promoters, which catalyzes trimethylation of lysine 27 on histone H3 (H3K27me3), thus promoting nucleosome assembly and suppressing gene expression. We found that an HIV-1 antisense transcript expressed from the 3'LTR and encoding the antisense protein ASP promotes proviral latency. Expression of ASP RNA reduced HIV-1 replication in Jurkat cells...
March 21, 2017: Virology
https://www.readbyqxmd.com/read/28323035/naturally-occurring-anti-cancer-agents-targeting-ezh2
#7
Fahimeh Shahabipour, Michele Caraglia, Muhammed Majeed, Giuseppe Derosa, Pamela Maffioli, Amirhossein Sahebkar
Natural products are considered as promising tools for the prevention and treatment of cancer. The enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase unit of polycomb repressor complexes such as PRC2 complex that has oncogenic roles through interference with growth and metastatic potential. Several agents targeting EZH2 has been discovered but they often induce side effects in clinical trials. Recently, EZH2 has emerged as a potential target of natural products with documented anti-cancer effects and this discloses a new scenario for the development of EZH2 inhibitory strategies with agents with low cytotoxic detrimental effects...
March 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28320739/a-covalently-bound-inhibitor-triggers-ezh2-degradation-through-chip-mediated-ubiquitination
#8
Xu Wang, Wei Cao, Jianjun Zhang, Ming Yan, Qin Xu, Xiangbing Wu, Lixin Wan, Zhiyuan Zhang, Chenping Zhang, Xing Qin, Meng Xiao, Dongxia Ye, Yuyang Liu, Zeguang Han, Shaomeng Wang, Li Mao, Wenyi Wei, Wantao Chen
Enhancer of zeste homolog 2 (EZH2) has been characterized as a critical oncogene and a promising drug target in human malignant tumors. The current EZH2 inhibitors strongly suppress the enhanced enzymatic function of mutant EZH2 in some lymphomas. However, the recent identification of a PRC2- and methyltransferase-independent role of EZH2 indicates that a complete suppression of all oncogenic functions of EZH2 is needed. Here, we report a unique EZH2-targeting strategy by identifying a gambogenic acid (GNA) derivative as a novel agent that specifically and covalently bound to Cys668 within the EZH2-SET domain, triggering EZH2 degradation through COOH terminus of Hsp70-interacting protein (CHIP)-mediated ubiquitination...
March 20, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28132848/vernalization-triggered-intragenic-chromatin-loop-formation-by-long-noncoding-rnas
#9
Dong-Hwan Kim, Sibum Sung
Long noncoding RNAs (lncRNAs) affect gene regulation through structural and regulatory interactions with associated proteins. The Polycomb complex often binds to lncRNAs in eukaryotes, and an lncRNA, COLDAIR, associates with Polycomb to mediate silencing of the floral repressor FLOWERING LOCUS C (FLC) during the process of vernalization in Arabidopsis. Here, we identified an additional Polycomb-binding lncRNA, COLDWRAP. COLDWRAP is derived from the repressed promoter of FLC and is necessary for the establishment of the stable repressed state of FLC by vernalization...
February 6, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28068325/trim28-interacts-with-ezh2-and-swi-snf-to-activate-genes-that-promote-mammosphere-formation
#10
J Li, Y Xi, W Li, R L McCarthy, S A Stratton, W Zou, W Li, S Y Dent, A K Jain, M C Barton
Histone methyl transferase EZH2 (Enhancer of Zeste Homolog 2) is generally associated with H3K27 methylation and gene silencing, as a member of the polycomb repressor 2 (PRC2) complex. Immunoprecipitation and mass spectrometry of the EZH2-protein interactome in estrogen receptor positive, breast cancer-derived MCF7 cells revealed EZH2 interactions with subunits of chromatin remodeler SWI/SNF complex and TRIM28, which formed a complex with EZH2 distinct from PRC2. Unexpectedly, transcriptome profiling showed that EZH2 primarily activates, rather than represses, transcription in MCF7 cells and with TRIM28 co-regulates a set of genes associated with stem cell maintenance and poor survival of breast cancer patients...
January 9, 2017: Oncogene
https://www.readbyqxmd.com/read/27932267/human-pre-pik3c2b-an-intronic-cis-element-with-dual-function-of-activation-and-repression
#11
Jayant Maini, Mohsen Ghasemi, Deepti Yandhuri, Suman S Thakur, Vani Brahmachari
The Polycomb/Trithorax Responsive Elements (PRE/TREs) are the cis-regulatory sequences that interact with both repressive (PcG) as well as activating (TrxG) complexes. However, most of the mammalian PREs are demonstrated to interact with the repressive polycomb (PcG) complexes only. We have carried out an unbiased search for proteins interacting with human PRE-PIK3C2B (hPRE-PIK3C2B) based on DNA affinity purification followed by mass spectrometry and identified MLL, MLL4 and WDR87 among other proteins in three biological replicates in HEK, U87 and HeLa cell lines...
December 6, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27898079/a-dna-element-that-remembers-winter
#12
Chenlong Li, Yuhai Cui
Polycomb-mediated silencing of the floral repressor gene FLC in response to long-term cold is a central event during vernalization in Arabidopsis thaliana, but how it is initiated is unclear. Two new studies identify a DNA element that mediates FLC silencing by attracting a pair of transcriptional repressors, VAL1 and VAL2, which in turn trigger epigenetic silencing by the Polycomb complex PHD-PRC2.
November 29, 2016: Nature Genetics
https://www.readbyqxmd.com/read/27856324/mll-af4-binds-directly-to-a-bcl-2-specific-enhancer-and-modulates-h3k27%C3%A2-acetylation
#13
Laura Godfrey, Jon Kerry, Ross Thorne, Emmanouela Repapi, James O J Davies, Marta Tapia, Erica Ballabio, Jim R Hughes, Huimin Geng, Marina Konopleva, Thomas A Milne
Survival rates for children and adults carrying mutations in the Mixed Lineage Leukemia (MLL) gene continue to have a very poor prognosis. The most common MLL mutation in acute lymphoblastic leukemia is the t(4;11)(q21;q23) chromosome translocation that fuses MLL in-frame with the AF4 gene producing MLL-AF4 and AF4-MLL fusion proteins. Previously, we found that MLL-AF4 binds to the BCL-2 gene and directly activates it through DOT1L recruitment and increased H3K79me2/3 levels. In the study described here, we performed a detailed analysis of MLL-AF4 regulation of the entire BCL-2 family...
March 2017: Experimental Hematology
https://www.readbyqxmd.com/read/27716060/mir-27b-shapes-the-presynaptic-transcriptome-and-influences-neurotransmission-by-silencing-the-polycomb-group-protein-bmi1
#14
Vivian Y Poon, Minxia Gu, Fang Ji, Antonius M VanDongen, Marc Fivaz
BACKGROUND: MicroRNAs (miRNAs) are short non-coding RNAs that are emerging as important post-transcriptional regulators of neuronal and synaptic development. The precise impact of miRNAs on presynaptic function and neurotransmission remains, however, poorly understood. RESULTS: Here, we identify miR-27b-an abundant neuronal miRNA implicated in neurological disorders-as a global regulator of the presynaptic transcriptome. miR-27b influences the expression of three quarters of genes associated with presynaptic function in cortical neurons...
October 4, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27705745/rybp-stimulates-prc1-to-shape-chromatin-based-communication-between-polycomb-repressive-complexes
#15
Nathan R Rose, Hamish W King, Neil P Blackledge, Nadezda A Fursova, Katherine Ji Ember, Roman Fischer, Benedikt M Kessler, Robert J Klose
Polycomb group (PcG) proteins function as chromatin-based transcriptional repressors that are essential for normal gene regulation during development. However, how these systems function to achieve transcriptional regulation remains very poorly understood. Here, we discover that the histone H2AK119 E3 ubiquitin ligase activity of Polycomb repressive complex 1 (PRC1) is defined by the composition of its catalytic subunits and is highly regulated by RYBP/YAF2-dependent stimulation. In mouse embryonic stem cells, RYBP plays a central role in shaping H2AK119 mono-ubiquitylation at PcG targets and underpins an activity-based communication between PRC1 and Polycomb repressive complex 2 (PRC2) which is required for normal histone H3 lysine 27 trimethylation (H3K27me3)...
October 5, 2016: ELife
https://www.readbyqxmd.com/read/27651832/fine-tuning-of-chromatin-composition-and-polycomb-recruitment-by-two-mi2-homologues-during-c-elegans-early-embryonic-development
#16
Stéphanie Käser-Pébernard, Catherine Pfefferli, Caroline Aschinger, Chantal Wicky
BACKGROUND: The nucleosome remodeling and deacetylase complex promotes cell fate decisions throughout embryonic development. Its core enzymatic subunit, the SNF2-like ATPase and Helicase Mi2, is well conserved throughout the eukaryotic kingdom and can be found in multiple and highly homologous copies in all vertebrates and some invertebrates. However, the reasons for such duplications and their implications for embryonic development are unknown. RESULTS: Here we studied the two C...
2016: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/27618650/the-long-noncoding-rna-chaer-defines-an-epigenetic-checkpoint-in-cardiac-hypertrophy
#17
Zhihua Wang, Xiao-Jing Zhang, Yan-Xiao Ji, Peng Zhang, Ke-Qiong Deng, Jun Gong, Shuxun Ren, Xinghua Wang, Iris Chen, He Wang, Chen Gao, Tomohiro Yokota, Yen Sin Ang, Shen Li, Ashley Cass, Thomas M Vondriska, Guangping Li, Arjun Deb, Deepak Srivastava, Huang-Tian Yang, Xinshu Xiao, Hongliang Li, Yibin Wang
Epigenetic reprogramming is a critical process of pathological gene induction during cardiac hypertrophy and remodeling, but the underlying regulatory mechanisms remain to be elucidated. Here we identified a heart-enriched long noncoding (lnc)RNA, named cardiac-hypertrophy-associated epigenetic regulator (Chaer), which is necessary for the development of cardiac hypertrophy. Mechanistically, Chaer directly interacts with the catalytic subunit of polycomb repressor complex 2 (PRC2). This interaction, which is mediated by a 66-mer motif in Chaer, interferes with PRC2 targeting to genomic loci, thereby inhibiting histone H3 lysine 27 methylation at the promoter regions of genes involved in cardiac hypertrophy...
October 2016: Nature Medicine
https://www.readbyqxmd.com/read/27557709/interdependence-of-prc1-and-prc2-for-recruitment-to-polycomb-response-elements
#18
Tatyana G Kahn, Eshagh Dorafshan, Dorothea Schultheis, Aman Zare, Per Stenberg, Ingolf Reim, Vincenzo Pirrotta, Yuri B Schwartz
Polycomb Group (PcG) proteins are epigenetic repressors essential for control of development and cell differentiation. They form multiple complexes of which PRC1 and PRC2 are evolutionary conserved and obligatory for repression. The targeting of PRC1 and PRC2 is poorly understood and was proposed to be hierarchical and involve tri-methylation of histone H3 (H3K27me3) and/or monoubiquitylation of histone H2A (H2AK118ub). Here, we present a strict test of this hypothesis using the Drosophila model. We discover that neither H3K27me3 nor H2AK118ub is required for targeting PRC complexes to Polycomb Response Elements (PREs)...
December 1, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27471304/arabidopsis-transcriptional-repressor-val1-triggers-polycomb-silencing-at-flc-during-vernalization
#19
Julia I Qüesta, Jie Song, Nuno Geraldo, Hailong An, Caroline Dean
The determinants that specify the genomic targets of Polycomb silencing complexes are still unclear. Polycomb silencing of Arabidopsis FLOWERING LOCUS C (FLC) accelerates flowering and involves a cold-dependent epigenetic switch. Here we identify a single point mutation at an intragenic nucleation site within FLC that prevents this epigenetic switch from taking place. The mutation blocks nucleation of plant homeodomain-Polycomb repressive complex 2 (PHD-PRC2) and indicates a role for the transcriptional repressor VAL1 in the silencing mechanism...
July 29, 2016: Science
https://www.readbyqxmd.com/read/27454161/bmi1-inhibits-senescence-and-enhances-the-immunomodulatory-properties-of-human-mesenchymal-stem-cells-via-the-direct-suppression-of-mkp-1-dusp1
#20
Jin Young Lee, Kyung-Rok Yu, Hyung-Sik Kim, Insung Kang, Jae-Jun Kim, Byung-Chul Lee, Soon Won Choi, Ji-Hee Shin, Yoojin Seo, Kyung-Sun Kang
For the application of mesenchymal stem cells (MSCs) as clinical therapeutics, the regulation of cellular aging is important to protect hMSCs from an age-associated decline in their function. In this study, we evaluated the effects of hypoxia on cellular senescence and the immunomodulatory abilities of hUCB-MSCs. Hypoxic-cultured hUCB-MSCs showed enhanced proliferation and had increased immunosuppressive effects on mitogen-induced mononuclear cell proliferation. We found that BMI1, a member of the polycomb repressive complex protein group, showed increased expression in hypoxic-cultured hUCB-MSCs, and the further knock-down of BMI1 in hypoxic cells induced decreased proliferative and immunomodulatory abilities in hUCB-MSCs, along with COX-2/PGE2 down-regulation...
August 2016: Aging
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