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https://www.readbyqxmd.com/read/28934594/noncoding-rnas-in-polycomb-and-trithorax-regulation-a-quantitative-perspective
#1
Leonie Ringrose
The question of how noncoding RNAs are involved in Polycomb group (PcG) and Trithorax group (TrxG) regulation has been on an extraordinary journey over the last three decades. Favored models have risen and fallen, and healthy debates have swept back and forth. The field has recently reached a critical mass of compelling data that throws light on several previously unresolved issues. The time is ripe for a fruitful combination of these findings with two other long-running avenues of research, namely the biochemical properties of the PcG/TrxG system and the application of theoretical mathematical models toward an understanding of the system's regulatory properties...
September 15, 2017: Annual Review of Genetics
https://www.readbyqxmd.com/read/28933484/long-non-coding-rna-snhg17-is-an-unfavourable-prognostic-factor-and-promotes-cell-proliferation-by-epigenetically-silencing-p57-in-colorectal-cancer
#2
Zhonghua Ma, Shengying Gu, Min Song, Changsheng Yan, Bingqing Hui, Hao Ji, Jirong Wang, Jianping Zhang, Keming Wang, Qinghong Zhao
Recently, substantial evidence has demonstrated that long non-coding RNAs (lncRNAs) play critical roles in multiple cancers including colorectal cancer (CRC). Utilizing publicly available lncRNA-expression-profiling data from the Gene Expression Omnibus (GEO) dataset GSE21510, we screened SNHG17 as a new candidate lncRNA associated with CRC development and progression. We further demonstrated that SNHG17 was upregulated in CRC tissues, and that its overexpression was significantly correlated with tumor size, TNM stage, and lymph node metastasis in CRC patients...
September 21, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28931748/participation-of-bmi-1-protein-in-cancer
#3
Agnieszka Zaczek, Paweł Jóźwiak, Anna Krześlak
BMI-1 (B-lymphoma Mo-MLV insertion region 1) protein is a constituent of Polycomb Repressive Complex 1 (PRC1) that via ubiquitination of histone H2A affects expression of many genes. BMI-1 is involved in cellular processes such as DNA repair, proliferation, growth, senescence and apoptosis. BMI-1 plays a key role in biology of stem cells including cancer stem cells by regulation of their self-renewal and differentiation. Accumulating evidence has revealed that overexpression of BMI-1 in many human cancers correlates with disease progression and therapy failure...
September 20, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28927461/additional-sex-combs-interacts-with-enhancer-of-zeste-and-trithorax-and-modulates-levels-of-trimethylation-on-histone-h3k4-and-h3k27-during-transcription-of-hsp70
#4
Taosui Li, Jacob W Hodgson, Svetlana Petruk, Alexander Mazo, Hugh W Brock
BACKGROUND: Maintenance of cell fate determination requires the Polycomb group for repression; the trithorax group for gene activation; and the enhancer of trithorax and Polycomb (ETP) group for both repression and activation. Additional sex combs (Asx) is a genetically identified ETP for the Hox loci, but the molecular basis of its dual function is unclear. RESULTS: We show that in vitro, Asx binds directly to the SET domains of the histone methyltransferases (HMT) enhancer of zeste [E(z)] (H3K27me3) and Trx (H3K4me3) through a bipartite interaction site separated by 846 amino acid residues...
September 19, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28924034/polycomb-directs-timely-activation-of-germline-genes-in-spermatogenesis
#5
So Maezawa, Kazuteru Hasegawa, Masashi Yukawa, Akihiko Sakashita, Kris G Alavattam, Paul R Andreassen, Miguel Vidal, Haruhiko Koseki, Artem Barski, Satoshi H Namekawa
During spermatogenesis, a large number of germline genes essential for male fertility are coordinately activated. However, it remains unknown how timely activation of this group of germline genes is accomplished. Here we show that Polycomb-repressive complex 1 (PRC1) directs timely activation of germline genes during spermatogenesis. Inactivation of PRC1 in male germ cells results in the gradual loss of a stem cell population and severe differentiation defects, leading to male infertility. In the stem cell population, RNF2, the dominant catalytic subunit of PRC1, activates transcription of Sall4, which codes for a transcription factor essential for subsequent spermatogenic differentiation...
September 18, 2017: Genes & Development
https://www.readbyqxmd.com/read/28919981/regulation-of-cancer-epigenomes-with-a-histone-binding-synthetic-transcription-factor
#6
David B Nyer, Rene M Daer, Daniel Vargas, Caroline Hom, Karmella A Haynes
Chromatin proteins have expanded the mammalian synthetic biology toolbox by enabling control of active and silenced states at endogenous genes. Others have reported synthetic proteins that bind DNA and regulate genes by altering chromatin marks, such as histone modifications. Previously, we reported the first synthetic transcriptional activator, the "Polycomb-based transcription factor" (PcTF) that reads histone modifications through a protein-protein interaction between the polycomb chromodomain motif and trimethylated lysine 27 of histone H3 (H3K27me3)...
2017: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/28916764/rapid-and-reversible-epigenome-editing-by-endogenous-chromatin-regulators
#7
Simon M G Braun, Jacob G Kirkland, Emma J Chory, Dylan Husmann, Joseph P Calarco, Gerald R Crabtree
Understanding the causal link between epigenetic marks and gene regulation remains a central question in chromatin biology. To edit the epigenome we developed the FIRE-Cas9 system for rapid and reversible recruitment of endogenous chromatin regulators to specific genomic loci. We enhanced the dCas9-MS2 anchor for genome targeting with Fkbp/Frb dimerizing fusion proteins to allow chemical-induced proximity of a desired chromatin regulator. We find that mSWI/SNF (BAF) complex recruitment is sufficient to oppose Polycomb within minutes, leading to activation of bivalent gene transcription in mouse embryonic stem cells...
September 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28914785/hsp90%C3%AE-mediates-bmi1-expression-in-breast-cancer-stem-progenitor-cells-through-facilitating-nuclear-translocation-of-c-myc-and-ezh2
#8
Yueh-Chun Lee, Wen-Wei Chang, Yi-Ying Chen, Yu-Hung Tsai, Ying-Hsiang Chou, Hsien-Chun Tseng, Hsin-Lin Chen, Chun-Chieh Wu, Ju Chang-Chien, Hsueh-Te Lee, Huei-Fan Yang, Bing-Yen Wang
Heat shock protein 90 (Hsp90) is a molecular chaperone that facilitates the correct folding and functionality of its client protein. Numerous Hsp90-client proteins are involved in cancer development. Thus, Hsp90 inhibitors have potential applications as anti-cancer drugs. We previously discovered that Hsp90α expression increased in breast cancer stem cells (BCSCs), which can initiate tumorigenesis and metastasis and resist treatment. In the present study, we further demonstrated that 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), an inhibitor of Hsp90, could suppress the self-renewal of BCSCs by downregulating B lymphoma Mo-MLV insertion region 1 homolog (BMI1), a polycomb family member with oncogenic activity in breast cancer...
September 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28912889/cbx8-suppresses-tumor-metastasis-via-repressing-snail-in-esophageal-squamous-cell-carcinoma
#9
Gang Wang, Jianjun Tang, Weixiang Zhan, Ruhua Zhang, Meifang Zhang, Dan Liao, Xin Wang, Yuanzhong Wu, Tiebang Kang
The poor clinical outcome and prognosis of esophageal squamous cell carcinoma (ESCC) is mainly attributed to its highly invasive and metastatic nature, making it urgent to further elicit the molecular mechanisms of the metastasis of ESCC. The function of each polycomb chromobox (CBX) protein in cancer is cell-type-dependent. Although CBX8 has been reported to promote the esophageal squamous cell carcinoma (ESCC) tumorigenesis, its role in ESCC metastasis has not been explored yet. In this study, we report that the inhibition of cell migration, invasion, and metastasis in ESCC requires CBX8-mediated repression of Snail, a key transcription factor that induces epithelial-to-mesenchymal transition (EMT), and that CBX8 inversely correlated with Snail in the ESCC tissues...
2017: Theranostics
https://www.readbyqxmd.com/read/28912479/late-stage-differentiation-of-embryonic-pancreatic-%C3%AE-cells-requires-jarid2
#10
Sara Cervantes, Marta Fontcuberta-PiSunyer, Joan-Marc Servitja, Rebeca Fernandez-Ruiz, Ainhoa García, Lidia Sanchez, Young-Sook Lee, Ramon Gomis, Rosa Gasa
Jarid2 is a component of the Polycomb Repressor complex 2 (PRC2), which is responsible for genome-wide H3K27me3 deposition, in embryonic stem cells. However, Jarid2 has also been shown to exert pleiotropic PRC2-independent actions during embryogenesis. Here, we have investigated the role of Jarid2 during pancreas development. Conditional ablation of Jarid2 in pancreatic progenitors results in reduced endocrine cell area at birth due to impaired endocrine cell differentiation and reduced prenatal proliferation...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28912427/dna-methylation-profiling-reveals-common-signatures-of-tumorigenesis-and-defines-epigenetic-prognostic-subtypes-of-canine-diffuse-large-b-cell-lymphoma
#11
Serena Ferraresso, Arianna Aricò, Tiziana Sanavia, Silvia Da Ros, Massimo Milan, Luciano Cascione, Stefano Comazzi, Valeria Martini, Mery Giantin, Barbara Di Camillo, Sandro Mazzariol, Diana Giannuzzi, Laura Marconato, Luca Aresu
Epigenetic deregulation is a hallmark of cancer characterized by frequent acquisition of new DNA methylation in CpG islands. To gain insight into the methylation changes of canine DLBCL, we investigated the DNA methylome in primary DLBCLs in comparison with control lymph nodes by genome-wide CpG microarray. We identified 1,194 target loci showing different methylation levels in tumors compared with controls. The hypermethylated CpG loci included promoter, 5'-UTRs, upstream and exonic regions. Interestingly, targets of polycomb repressive complex in stem cells were mostly affected suggesting that DLBCL shares a stem cell-like epigenetic pattern...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28912274/structure-mechanism-and-regulation-of-polycomb-repressive-complex-2
#12
Lindsay E Moritz, Raymond C Trievel
Polycomb Repressive Complex 2 (PRC2) methylates lysine 27 in histone H3, a modification associated with epigenetic gene silencing. This complex plays a fundamental role in regulating cellular differentiation and development, and PRC2 overexpression and mutations have been implicated in numerous cancers. In this review, we examine recent studies elucidating the first crystal structures of the PRC2 core complex, yielding seminal insights into its catalytic mechanism, substrate specificity, allosteric regulation, and inhibition by a class of small molecules that are currently undergoing cancer clinical trials...
September 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28910569/hierarchical-recruitment-of-polycomb-complexes-revisited
#13
Eshagh Dorafshan, Tatyana G Kahn, Yuri B Schwartz
Polycomb Group (PcG) proteins epigenetically repress key developmental genes and thereby control alternative cell fates. PcG proteins act as complexes that can modify histones and these histone modifications play a role in transmitting the "memory" of the repressed state as cells divide. Here we consider mainstream models that link histone modifications to hierarchical recruitment of PcG complexes and compare them to results of a direct test of interdependence between PcG complexes for recruitment to Drosophila genes...
September 14, 2017: Nucleus
https://www.readbyqxmd.com/read/28910411/molecular-population-genetics-of-the-polycomb-genes-in-drosophila-subobscura
#14
Juan M Calvo-Martín, Montserrat Papaceit, Carmen Segarra
Polycomb group (PcG) proteins are important regulatory factors that modulate the chromatin state. They form protein complexes that repress gene expression by the introduction of posttranslational histone modifications. The study of PcG proteins divergence in Drosophila revealed signals of coevolution among them and an acceleration of the nonsynonymous evolutionary rate in the lineage ancestral to the obscura group species, mainly in subunits of the Pcl-PRC2 complex. Herein, we have studied the nucleotide polymorphism of PcG genes in a natural population of D...
2017: PloS One
https://www.readbyqxmd.com/read/28904641/histone-code-and-long-non-coding-rnas-lncrnas-aberrations-in-lung-cancer-implications-in-the-therapy-response
#15
REVIEW
Abril Marcela Herrera-Solorio, Leonel Armas-López, Oscar Arrieta, Joaquín Zúñiga, Patricia Piña-Sánchez, Federico Ávila-Moreno
Respiratory diseases hold several genome, epigenome, and transcriptional aberrations as a cause of the accumulated damage promoted by, among others, environmental risk factors. Such aberrations can also come about as an adaptive response when faced with therapeutic oncological drugs. In epigenetic terms, aberrations in DNA methylation patterns, histone code marks balance, and/or chromatin-remodeling complexes recruitment, among Polycomb Repressive Complex-2 (PRC2) versus Trithorax (TRX) Activator Complex, have been proposed to be affected by several previously characterized functional long non-coding RNAs (lncRNAs)...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28901436/taurine%C3%A2-upregulated-gene-1-a-vital-long-non%C3%A2-coding-rna-associated-with-cancer-in-humans-review
#16
Wen-Yu Wang, Yan-Fen Wang, Pei Ma, Tong-Peng Xu, Yong-Qian Shu
It is widely reported that long non‑coding RNAs (lncRNAs) are involved in regulating cell differentiation, proliferation, apoptosis and other biological processes. Certain lncRNAs have been found to be crucial in various types of tumor. Taurine‑upregulated gene 1 (TUG1) has been shown to be expressed in a tissue‑specific pattern and exert oncogenic or tumor suppressive functions in different types of cancer in humans. According to previous studies, TUG1 is predominantly located in the nucleus and may regulate gene expression at the transcriptional level...
September 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28900001/samd7-is-a-cell-type-specific-prc1-component-essential-for-establishing-retinal-rod-photoreceptor-identity
#17
Yoshihiro Omori, Shun Kubo, Tetsuo Kon, Mayu Furuhashi, Hirotaka Narita, Taro Kominami, Akiko Ueno, Ryotaro Tsutsumi, Taro Chaya, Haruka Yamamoto, Isao Suetake, Shinji Ueno, Haruhiko Koseki, Atsushi Nakagawa, Takahisa Furukawa
Precise transcriptional regulation controlled by a transcription factor network is known to be crucial for establishing correct neuronal cell identities and functions in the CNS. In the retina, the expression of various cone and rod photoreceptor cell genes is regulated by multiple transcription factors; however, the role of epigenetic regulation in photoreceptor cell gene expression has been poorly understood. Here, we found that Samd7, a rod-enriched sterile alpha domain (SAM) domain protein, is essential for silencing nonrod gene expression through H3K27me3 regulation in rod photoreceptor cells...
September 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28898989/role-of-histone-h3k27-trimethylation-loss-as-a-marker-for-malignant-peripheral-nerve-sheath-tumor-in-fine-needle-aspiration-and-small-biopsy-specimens
#18
Jeffrey K Mito, Xiaohua Qian, Leona A Doyle, Jason L Hornick, Vickie Y Jo
Objectives: Accurate diagnosis of malignant peripheral nerve sheath tumor (MPNST) is often challenging on fine-needle aspiration (FNA) or core needle biopsy. Recurrent mutations in EED and SUZ12, which encode subunits of polycomb repressive complex 2 (PRC2), have been identified in 70% to 92% of MPNSTs; PRC2 inactivation leads to loss of trimethylation of lysine 27 of histone H3 (H3K27me3). We evaluated the utility of H3K27me3 immunohistochemistry for distinguishing MPNST from its cytomorphologic mimics...
August 1, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28898712/inhibition-of-the-lytic-cycle-of-kaposi-s-sarcoma-associated-herpesvirus-by-cohesin-factors-following-de-novo-infection
#19
Zsolt Toth, Richard J Smindak, Bernadett Papp
Establishment of Kaposi's sarcoma-associated herpesvirus (KSHV) latency following infection is a multistep process, during which polycomb proteins are recruited onto the KSHV genome, which is crucial for the genome-wide repression of lytic genes during latency. Strikingly, only a subset of lytic genes are expressed transiently in the early phase of infection prior to the binding of polycomb proteins onto the KSHV genome, which raises the question what restricts lytic gene expression in the first hours of infection...
September 9, 2017: Virology
https://www.readbyqxmd.com/read/28898697/chronic-cigarette-smoke-induced-epigenomic-changes-precede-sensitization-of-bronchial-epithelial-cells-to-single-step-transformation-by-kras-mutations
#20
Michelle Vaz, Stephen Y Hwang, Ioannis Kagiampakis, Jillian Phallen, Ashwini Patil, Heather M O'Hagan, Lauren Murphy, Cynthia A Zahnow, Edward Gabrielson, Victor E Velculescu, Hariharan P Easwaran, Stephen B Baylin
We define how chronic cigarette smoke-induced time-dependent epigenetic alterations can sensitize human bronchial epithelial cells for transformation by a single oncogene. The smoke-induced chromatin changes include initial repressive polycomb marking of genes, later manifesting abnormal DNA methylation by 10 months. At this time, cells exhibit epithelial-to-mesenchymal changes, anchorage-independent growth, and upregulated RAS/MAPK signaling with silencing of hypermethylated genes, which normally inhibit these pathways and are associated with smoking-related non-small cell lung cancer...
September 11, 2017: Cancer Cell
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