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https://www.readbyqxmd.com/read/28436983/stable-polycomb-dependent-transgenerational-inheritance-of-chromatin-states-in-drosophila
#1
Filippo Ciabrelli, Federico Comoglio, Simon Fellous, Boyan Bonev, Maria Ninova, Quentin Szabo, Anne Xuéreb, Christophe Klopp, Alexei Aravin, Renato Paro, Frédéric Bantignies, Giacomo Cavalli
Transgenerational epigenetic inheritance (TEI) describes the transmission of alternative functional states through multiple generations in the presence of the same genomic DNA sequence. Very little is known about the principles and the molecular mechanisms governing this type of inheritance. Here, by transiently enhancing 3D chromatin interactions, we established stable and isogenic Drosophila epilines that carry alternative epialleles, as defined by differential levels of Polycomb-dependent trimethylation of histone H3 Lys27 (forming H3K27me3)...
April 24, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28436944/active-and-poised-promoter-states-drive-folding-of-the-extended-hoxb-locus-in-mouse-embryonic-stem-cells
#2
Mariano Barbieri, Sheila Q Xie, Elena Torlai Triglia, Andrea M Chiariello, Simona Bianco, Inês de Santiago, Miguel R Branco, David Rueda, Mario Nicodemi, Ana Pombo
Gene expression states influence the 3D conformation of the genome through poorly understood mechanisms. Here, we investigate the conformation of the murine HoxB locus, a gene-dense genomic region containing closely spaced genes with distinct activation states in mouse embryonic stem (ES) cells. To predict possible folding scenarios, we performed computer simulations of polymer models informed with different chromatin occupancy features that define promoter activation states or binding sites for the transcription factor CTCF...
April 24, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28435537/integrated-platform-for-expedited-synthesis-purification-testing-of-small-molecule-libraries
#3
Aleksandra Baranczak, Noah P Tu, Jasmina Marjanovic, Philip A Searle, Anil Vasudevan, Stevan W Djuric
The productivity of medicinal chemistry programs can be significantly increased through the introduction of automation, leading to shortened discovery cycle times. Herein, we describe a platform that consolidates synthesis, purification, quantitation, dissolution, and testing of small molecule libraries. The system was validated through the synthesis and testing of two libraries of binders of polycomb protein EED, and excellent correlation of obtained data with results generated through conventional approaches was observed...
April 13, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28434938/polycomb-group-gene-e-z-is-required-for-spermatogonial-dedifferentiation-in-drosophila-adult-testis
#4
Suk Ho Eun, Lijuan Feng, Luis Cedeno-Rosario, Qiang Gan, Gang Wei, Kairong Cui, Keji Zhao, Xin Chen
Dedifferentiation is an important process to replenish lost stem cells during aging or regeneration after injury to maintain tissue homeostasis. Here we report that Enhancer of Zeste [E(z)], a component of the Polycomb Repression Complex 2 (PRC2), is required to maintain a stable pool of germline stem cells (GSCs) within the niche microenvironment. During aging, germ cells with reduced E(z) activity cannot meet that requirement, but the defect neither arises from increased GSC death nor premature differentiation...
April 20, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28433419/disconnect-between-alcohol-induced-alterations-in-chromatin-structure-and-gene-transcription-in-a-mouse-embryonic-stem-cell-model-of-exposure
#5
Kylee J Veazey, Haiqing Wang, Yudhishtar S Bedi, William M Skiles, Richard Cheng-An Chang, Michael C Golding
Alterations to chromatin structure induced by environmental insults have become an attractive explanation for the persistence of exposure effects into subsequent life stages. However, a growing body of work examining the epigenetic impact that alcohol and other drugs of abuse exert consistently notes a disconnection between induced changes in chromatin structure and patterns of gene transcription. Thus, an important question is whether perturbations in the 'histone code' induced by prenatal exposures to alcohol implicitly subvert gene expression, or whether the hierarchy of cellular signaling networks driving development is such that they retain control over the transcriptional program...
January 11, 2017: Alcohol
https://www.readbyqxmd.com/read/28428341/ctf4-related-protein-recruits-lhp1-prc2-to-maintain-h3k27me3-levels-in-dividing-cells-in-arabidopsis-thaliana
#6
Yue Zhou, Emmanuel Tergemina, Haitao Cui, Alexander Förderer, Benjamin Hartwig, Geo Velikkakam James, Korbinian Schneeberger, Franziska Turck
Polycomb Repressive Complex (PRC) 2 catalyzes the H3K27me3 modification that warrants inheritance of a repressive chromatin structure during cell division, thereby assuring stable target gene repression in differentiated cells. It is still under investigation how H3K27me3 is passed on from maternal to filial strands during DNA replication; however, cell division can reinforce H3K27me3 coverage at target regions. To identify novel factors involved in the Polycomb pathway in plants, we performed a forward genetic screen for enhancers of the like heterochromatin protein 1 (lhp1) mutant, which shows relatively mild phenotypic alterations compared with other plant PRC mutants...
April 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28426098/targeting-chromatin-defects-in-selected-solid-tumors-based-on-oncogene-addiction-synthetic-lethality-and-epigenetic-antagonism
#7
D Morel, G Almouzni, J-C Soria, S Postel-Vinay
Background: Although the role of epigenetic abnormalities has been studied for several years in cancer genesis and development, epigenetic-targeting drugs have historically failed to demonstrate efficacy in solid malignancies. However, successful targeting of chromatin remodeling deficiencies, histone writers and histone reader alterations has been achieved very recently using biomarker-driven and mechanism-based approaches. Epigenetic targeting is now one of the most active areas in drug development and could represent novel therapeutic opportunity for up to 25% of all solid tumors...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28425347/expression-and-clinicopathological-significance-of-mel-18-and-bmi-1-in-esophageal-squamous-cell-carcinoma
#8
Huaijun Ji, Ming Cao, Kunlun Ren, Ningbo Sun, Wei Wang, Qiang Zhu, Qi Zang, Zhongmin Jiang
The Polycomb group genes are a general class of regulators that are responsible for maintaining homeotic gene expression throughout cell division. Polycomb group expression plays an important role in oncogenesis of several types of human cancer. Melanoma nuclear protein 18 and B-cell-specific Moloney leukemia virus insert site 1 are key Polycomb group proteins. Studies have shown that melanoma nuclear protein 18 is a potential tumor suppression, and B-cell-specific Moloney leukemia virus insert site 1 is overexpressed in several human malignancies...
January 1, 2017: Technology in Cancer Research & Treatment
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
#9
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/28421446/pre-tre-elements-act-as-transcription-activators-in-drosophila-s2-cells
#10
D A Chetverina, A V Mikhailova, P G Georgiev, M M Erokhin
The Drosophila PRE/TRE elements are DNA targets for Polycomb and Trithorax group proteins, which control repression and activation of gene transcription, respectively. In this study, we show that, in transiently transfected Drosophila S2 cells, bxdPRE activates transcription driven from different promoters. Using CG32795 gene promoter, we demonstrate that other PRE/TRE elements-Fab7, en, eve, and CycB-also act as transcription activators in this model system.
January 2017: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28416772/dna-methylation-of-mettl7a-gene-body-regulates-its-transcriptional-level-in-thyroid-cancer
#11
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
#12
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/28414199/structure-of-the-prc2-complex-and-application-to-drug-discovery
#13
REVIEW
Yi Shi, Xiao-Xi Wang, You-Wen Zhuang, Yi Jiang, Karsten Melcher, H Eric Xu
The polycomb repressive complexes 2 (PRC2) complex catalyzes tri-methylation of histone H3 lysine 27 (H3K27), a repressive chromatin marker associated with gene silencing. Overexpression and mutations of PRC2 are found in a wide variety of cancers, making the catalytic activity of PRC2 an important target of cancer therapy. This review highlights recent structural breakthroughs of the human PRC2 complex bound to the H3K27 peptide and a small molecule inhibitor, which provide critically needed insight into PRC2-targeted drug discovery...
April 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28412742/association-of-the-long-non-coding-rna-malat1-with-the-polycomb-repressive-complex-pathway-in-t-and-nk-cell-lymphoma
#14
Soo Hee Kim, Se Hoon Kim, Woo Ick Yang, Soo Jeong Kim, Sun Och Yoon
Recently, various long non-coding RNAs (lncRNAs) have been reported to have significant therapeutic or prognostic value. However, the expression of lncRNAs has not been investigated in T and NK cell lymphoma. Thus, we evaluated the biological and prognostic role of lncRNAs related to the polycomb repressive complex (PRC) and PRC markers in tissue samples and cell lines of T and NK cell lymphoma. Among the tested lncRNAs, MALAT1 was most highly expressed in clinical samples and cell lines. High expression of MALAT1 as well as BMI1 was related to poor prognosis in patients with mature T cell lymphoma...
February 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410989/polycomb-repressive-complex-2-mediated-chromatin-repression-guides-effector-cd8-t-cell-terminal-differentiation-and-loss-of-multipotency
#15
Simon M Gray, Robert A Amezquita, Tianxia Guan, Steven H Kleinstein, Susan M Kaech
Understanding immunological memory formation depends on elucidating how multipotent memory precursor (MP) cells maintain developmental plasticity and longevity to provide long-term immunity while other effector cells develop into terminally differentiated effector (TE) cells with limited survival. Profiling active (H3K27ac) and repressed (H3K27me3) chromatin in naive, MP, and TE CD8(+) T cells during viral infection revealed increased H3K27me3 deposition at numerous pro-memory and pro-survival genes in TE relative to MP cells, indicative of fate restriction, but permissive chromatin at both pro-memory and pro-effector genes in MP cells, indicative of multipotency...
April 18, 2017: Immunity
https://www.readbyqxmd.com/read/28410242/functional-and-therapeutic-significance-of-ezh2-in-urological-cancers
#16
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/28406475/depletion-of-polycomb-repressive-complex-2-core-component-eed-impairs-fetal-hematopoiesis
#17
Wenhua Yu, Fang Zhang, Shiyan Wang, Yi Fu, Jiahuan Chen, Xiaodong Liang, Huangying Le, William T Pu, Bing Zhang
Polycomb repressive complex 2 (PRC2), a H3K27me3 methyltransferase complex, promotes the development of many organs by silencing ectopic transcription program. However, currently little is known about the role of PRC2 in blood and vascular development. In this study, we interrogated the function of embryonic ectoderm development (EED), a core PRC2 component, in both endothelial and hematopoietic tissues by inactivating a floxed murine EED allele with Tie2Cre, which catalyzes recombination in endothelial and hematopoietic lineages...
April 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28403905/h2a-monoubiquitination-in-arabidopsis-thaliana-is-generally-independent-of-lhp1-and-prc2-activity
#18
Yue Zhou, Francisco J Romero-Campero, Ángeles Gómez-Zambrano, Franziska Turck, Myriam Calonje
BACKGROUND: Polycomb group complexes PRC1 and PRC2 repress gene expression at the chromatin level in eukaryotes. The classic recruitment model of Polycomb group complexes in which PRC2-mediated H3K27 trimethylation recruits PRC1 for H2A monoubiquitination was recently challenged by data showing that PRC1 activity can also recruit PRC2. However, the prevalence of these two mechanisms is unknown, especially in plants as H2AK121ub marks were examined at only a handful of Polycomb group targets...
April 12, 2017: Genome Biology
https://www.readbyqxmd.com/read/28401191/inhibition-of-ezh2-degradation-as-a-novel-approach-to-overcome-drug-resistance-in-acute-myeloid-leukemia
#19
Stefanie Göllner, Carsten Müller-Tidow
The polycomb protein enhancer of zeste homolog 2 (EZH2) may have a dual role in cancer pathogenesis acting as an oncogene or as a tumor suppressor depending on the cancer type. We recently demonstrated that proteasomal degradation of EZH2 resulting from cyclin-dependent kinase 1 (CDK1)-induced phosphorylation at Threonine (T) 487 represents a novel mechanism of drug resistance in acute myeloid leukemia (AML). Our findings suggest that restoration of EZH2 protein is a viable approach to overcome therapy resistance in AML...
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28394339/nspc1-promotes-cancer-stem-cell-self-renewal-by-repressing-the-synthesis-of-all-trans-retinoic-acid-via-targeting-rdh16-in-malignant-glioma
#20
P-S Hu, Q-S Xia, F Wu, D-K Li, Y-J Qi, Y Hu, Z-Z Wei, S-S Li, N-Y Tian, Q-F Wei, L-J Shen, B Yin, T Jiang, J-G Yuan, B-Q Qiang, W Han, X-Z Peng
Polycomb group (PcG) proteins play an important role in development and stem cell maintenance, and their dysregulation have been closely linked to oncogenesis and cancer stem cell phenotypes. Here, we found that nervous system polycomb 1 (NSPc1) was highly expressed in stem cell-like glioma cells (SLCs). Knockdown of NSPc1 in SLCs resulted in impaired neurosphere formation and self-renewal abilities, down-regulated expression of stemness markers such as NESTIN, CD133 and SOX2, and decreased capacity to propagate subcutaneous xenografts...
April 10, 2017: Oncogene
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