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https://www.readbyqxmd.com/read/28818970/dna-replication-coupled-histone-modification-maintains-polycomb-gene-silencing-in-plants
#1
Danhua Jiang, Frédéric Berger
Propagation of patterns of gene expression through the cell cycle requires prompt restoration of epigenetic marks after the twofold dilution caused by DNA replication. Here, we show that the transcriptional repressive mark histone H3 lysine 27 trimethylation (H3K27me3) is restored in replicating plant cells through DNA replication-coupled modification of histone variant H3.1. Plants evolved a mechanism for efficient K27 trimethylation on H3.1, which is essential for inheritance of the silencing memory from mother to daughter cells...
August 17, 2017: Science
https://www.readbyqxmd.com/read/28818969/distinct-phases-of-polycomb-silencing-to-hold-epigenetic-memory-of-cold-in-arabidopsis
#2
Hongchun Yang, Scott Berry, Tjelvar S G Olsson, Matthew Hartley, Martin Howard, Caroline Dean
Gene silencing by Polycomb complexes is central to eukaryotic development. Cold-induced epigenetic repression of FLOWERING LOCUS C (FLC) in the plant Arabidopsis provides an opportunity to study initiation and maintenance of Polycomb silencing. Here, we show that a subset of Polycomb Repressive Complex 2 factors nucleate silencing in a small region within FLC, locally increasing H3K27me3 levels. This nucleation confers a silenced state that is metastably inherited, with memory held in the local chromatin. Metastable memory is then converted to stable epigenetic silencing through separate Polycomb factors, which spread across the locus after cold to enlarge the domain containing H3K27me3...
August 17, 2017: Science
https://www.readbyqxmd.com/read/28811977/epigenetic-regulation-of-the-extrinsic-oncosuppressor-ptx3-gene-in-inflammation-and-cancer
#3
Marcello Rubino, Paolo Kunderfranco, Gianluca Basso, Carolina Magdalen Greco, Fabio Pasqualini, Simone Serio, Massimo Roncalli, Luigi Laghi, Alberto Mantovani, Roberto Papait, Cecilia Garlanda
PTX3 is a component of the humoral arm of innate immunity and an extrinsic oncosuppressor gene taming tumor-promoting inflammation. Here, we show that two enhancers differently regulate PTX3 expression: enhancer 1, located 230 kb upstream of PTX3 promoter, mediated the action of inflammatory transcription factors; and enhancer 2, encompassing PTX3 second exon, was implicated in pre-initiation complex assembly. Polycomb repressive complex 2 silenced these regulatory elements and the promoter in basal condition...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28810646/sex-comb-on-midleg-like-2-is-a-novel-specific-marker-for-the-diagnosis-of-gastroenteropancreatic-neuroendocrine-tumors
#4
Jiao-Jiao Yang, Hua Huang, Ming-Bing Xiao, Feng Jiang, Wen-Kai Ni, Yi-Fei Ji, Cui-Hua Lu, Run-Zhou Ni
Sex comb on midleg like-2 (SCML2) is a polycomb-group protein that encodes transcriptional repressors essential for appropriate development in the fly and in mammals. On the basis of previous findings, the present study aimed to explore the possibility of developing SCML2 into a new diagnostic marker for gastroenteropancreatic neuroendocrine tumors (GEP-NETs). A total of 64 paired GEP-NET tissues and adjacent non-tumorous tissues were obtained from patients who had undergone surgical resection between January 2009 and January 2014, and the expression of SCML2 and two neuroendocrine markers, namely synaptophysin (Syn) and chromogranin A (CgA), in the tissues was assessed by immunohistochemistry...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28808113/lncrna-gas5-inhibits-microglial-m2-polarization-and-exacerbates-demyelination
#5
Dingya Sun, Zhongwang Yu, Xue Fang, Mingdong Liu, Yingyan Pu, Qi Shao, Dan Wang, Xiaolin Zhao, Aijun Huang, Zhenghua Xiang, Chao Zhao, Robin Jm Franklin, Li Cao, Cheng He
The regulation of inflammation is pivotal for preventing the development or reoccurrence of multiple sclerosis (MS). A biased ratio of high-M1 versus low-M2 polarized microglia is a major pathological feature of MS Here, using microarray screening, we identify the long noncoding RNA (lncRNA) GAS5 as an epigenetic regulator of microglial polarization. Gain- and loss-of-function studies reveal that GAS5 suppresses microglial M2 polarization. Interference with GAS5 in transplanted microglia attenuates the progression of experimental autoimmune encephalomyelitis (EAE) and promotes remyelination in a lysolecithin-induced demyelination model...
August 14, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28808080/characterization-of-the-human-thyroid-epigenome
#6
Celia Siu, Sam Michael Wiseman, Sitanshu Gakkhar, Alireza Heravi-Moussavi, Misha Bilenky, Annaick Carles, Thomas Sierocinski, Angela Tam, Eric Yang Zhao, Katayoon Kasaian, Richard A Moore, Andrew J Mungall, Blair Walker, Thomas Thomson, Marco A Marra, Martin Hirst, Steven Jones
The thyroid gland, necessary for normal human growth and development, functions as an essential regulator of metabolism by the production and secretion of appropriate levels of thyroid hormone. However, assessment of abnormal thyroid function may be challenging suggesting a more fundamental understanding of normal function is needed. One way to characterize normal gland function is to study the epigenome and resulting transcriptome within its constituent cells. This study generates the first published reference epigenomes for human thyroid from four individuals using ChIP-seq and RNA-seq...
August 14, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28801151/correlation-between-desiccation-stress-response-and-epigenetic-modifications-of-genes-in-drosophila-melanogaster-an-example-of-environment-epigenome-interaction
#7
Vineeta Sharma, Surbhi Kohli, Vani Brahmachari
Animals from different phyla including arthropods tolerate water stress to different extent. This tolerance is accompanied by biochemical changes which in turn are due to transcriptional alteration. The changes in transcription can be an indirect effect on some of the genes, ensuing from the effect of stress on the regulators of transcription including epigenetic regulators. Within this paradigm, we investigated the correlation between stress response and epigenetic modification underlying gene expression modulation during desiccation stress in Canton-S...
August 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28796262/long-noncoding-rna-crnde-promotes-colorectal-cancer-cell-proliferation-via-epigenetically-silencing-dusp5-cdkn1a-expression
#8
Jie Ding, Juan Li, HaiYan Wang, Yun Tian, Min Xie, XueZhi He, Hao Ji, Zhonghua Ma, Bingqing Hui, Keming Wang, Guozhong Ji
Evidence indicates that long non-coding RNAs (lncRNAs) play a critical role in the regulation of tumor cellular processes, such as proliferation, apoptosis, and metastasis. LncRNA CRNDE (Colorectal Neoplasia Differentially Expressed) is located at human chromosome 16 and has been found overexpressed in a variety of cancers including colorectal cancer (CRC). In this paper, we report that lncRNA CRNDE expression was remarkably upregulated in CRC tissues and that lncRNA CRNDE overexpression was positively correlated with advanced pathological stages and larger tumor sizes...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28782042/polycomb-repressive-complex-1-modifies-transcription-of-active-genes
#9
Michelle Pherson, Ziva Misulovin, Maria Gause, Kathie Mihindukulasuriya, Amanda Swain, Dale Dorsett
This study examines the role of Polycomb repressive complex 1 (PRC1) at active genes. The PRC1 and PRC2 complexes are crucial for epigenetic silencing during development of an organism. They are recruited to Polycomb response elements (PREs) and establish silenced domains over several kilobases. Recent studies show that PRC1 is also directly recruited to active genes by the cohesin complex. Cohesin participates broadly in control of gene transcription, but it is unknown whether cohesin-recruited PRC1 also plays a role in transcriptional control of active genes...
August 2017: Science Advances
https://www.readbyqxmd.com/read/28780076/bmi1-and-mel18-promote-colitis-associated-cancer-in-mice-via-reg3b-and-stat3
#10
Xicheng Liu, Wendi Wei, Xiaowei Li, Pengcheng Shen, Dapeng Ju, Zhen Wang, Rukui Zhang, Fu Yang, Chunyan Chen, Kun Cao, Guoli Zhu, Hongyan Chen, Liang Chen, Jianhua Sui, Erquan Zhang, Kaichun Wu, Fengchao Wang, Liping Zhao, Rongwen Xi
BACKGROUND & AIMS: Polycomb group proteins are epigenetic factors that silence gene expression; they are dysregulated in cancer cells and contribute to carcinogenesis by unclear mechanisms. We investigated whether BMI1 proto-oncogene, polycomb ring finger (BMI1) and polycomb group ring finger 2 (PCGF2, also called MEL18) are involved in initiation and progression of colitis-associated cancer (CAC) in mice. METHODS: We generated mice containing floxed alleles of Bmi1 and/or Mel18 and/or Reg3b using the villin-Cre promoter (called Bmi1(ΔIEC), Mel18(ΔIEC), DKO, and TKO mice)...
August 2, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28768204/single-cell-landscape-of-transcriptional-heterogeneity-and-cell-fate-decisions-during-mouse-early-gastrulation
#11
Hisham Mohammed, Irene Hernando-Herraez, Aurora Savino, Antonio Scialdone, Iain Macaulay, Carla Mulas, Tamir Chandra, Thierry Voet, Wendy Dean, Jennifer Nichols, John C Marioni, Wolf Reik
The mouse inner cell mass (ICM) segregates into the epiblast and primitive endoderm (PrE) lineages coincident with implantation of the embryo. The epiblast subsequently undergoes considerable expansion of cell numbers prior to gastrulation. To investigate underlying regulatory principles, we performed systematic single-cell RNA sequencing (seq) of conceptuses from E3.5 to E6.5. The epiblast shows reactivation and subsequent inactivation of the X chromosome, with Zfp57 expression associated with reactivation and inactivation together with other candidate regulators...
August 1, 2017: Cell Reports
https://www.readbyqxmd.com/read/28765367/polycomb-mediated-chromatin-loops-revealed-by-a-subkilobase-resolution-chromatin-interaction-map
#12
Kyle P Eagen, Erez Lieberman Aiden, Roger D Kornberg
The locations of chromatin loops in Drosophila were determined by Hi-C (chemical cross-linking, restriction digestion, ligation, and high-throughput DNA sequencing). Whereas most loop boundaries or "anchors" are associated with CTCF protein in mammals, loop anchors in Drosophila were found most often in association with the polycomb group (PcG) protein Polycomb (Pc), a subunit of polycomb repressive complex 1 (PRC1). Loops were frequently located within domains of PcG-repressed chromatin. Promoters located at PRC1 loop anchors regulate some of the most important developmental genes and are less likely to be expressed than those not at PRC1 loop anchors...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28762137/a-clinicopathologic-study-of-head-and-neck-malignant-peripheral-nerve-sheath-tumors
#13
Adepitan A Owosho, Cherry L Estilo, Joseph M Huryn, Ping Chi, Cristina R Antonescu
Head and neck high grade malignant peripheral nerve sheath tumors (HN-MPNSTs) are rare highly aggressive soft tissue sarcomas that show overlapping morphologic and immunophenotypic features with melanoma and other high grade sarcomas, resulting in diagnostic challenges, particularly in sporadic settings. Recent discoveries have implicated loss of function mutations in the polycomb repressive complex 2 (PRC2) components, including EED or SUZ12 genes, as one of the leading pathogenetic mechanisms in high grade MPNST...
July 31, 2017: Head and Neck Pathology
https://www.readbyqxmd.com/read/28761084/single-vector-non-leaky-gene-expression-system-for-drosophila-melanogaster
#14
Arslan Akmammedov, Marco Geigges, Renato Paro
An ideal transgenic gene expression system is inducible, non-leaky, and well tolerated by the target organism. While the former has been satisfactorily realized, leakiness and heavy physiological burden imposed by the existing systems are still prominent hurdles in their successful implementation. Here we describe a new system for non-leaky expression of transgenes in Drosophila. PRExpress is based on a single transgenic construct built from endogenous components, the inducible hsp70 promoter and a multimerized copy of a Polycomb response element (PRE) controlled by epigenetic chromatin regulators of the Polycomb group...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28759577/modular-function-of-long-noncoding-rna-coldair-in-the-vernalization-response
#15
Dong-Hwan Kim, Yanpeng Xi, Sibum Sung
The long noncoding RNA COLDAIR is necessary for the repression of a floral repressor FLOWERING LOCUS C (FLC) during vernalization in Arabidopsis thaliana. The repression of FLC is mediated by increased enrichment of Polycomb Repressive Complex 2 (PRC2) and subsequent trimethylation of Histone H3 Lysine 27 (H3K27me3) at FLC chromatin. In this study we found that the association of COLDAIR with chromatin occurs only at the FLC locus and that the central region of the COLDAIR transcript is critical for this interaction...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28758948/polycomb-repressor-complex-2-in-genomic-instability-and-cancer
#16
REVIEW
Zoe Veneti, Kalliopi K Gkouskou, Aristides G Eliopoulos
Polycomb repressor complexes PRC1 and PRC2 regulate chromatin compaction and gene expression, and are widely recognized for their fundamental contributions to developmental processes. Herein, we summarize the existing evidence and molecular mechanisms linking PRC-mediated epigenetic aberrations to genomic instability and malignancy, with a particular focus on the role of deregulated PRC2 in tumor suppressor gene expression, the DNA damage response, and the fidelity of DNA replication. We also discuss some of the recent advances in the development of pharmacological and dietary interventions affecting PRC2, which point to promising applications for the prevention and management of human malignancies...
July 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28758277/fusion-of-the-genes-brd8-and-phf1-in-endometrial-stromal-sarcoma
#17
Francesca Micci, Marta Brunetti, Paola Dal Cin, Marisa R Nucci, Ludmila Gorunova, Sverre Heim, Ioannis Panagopoulos
We present a new endometrial stromal sarcoma (ESS)-associated genomic rearrangement involving chromosome arms 5p and 6p and leading to the formation of a BRD8-PHF1 fusion gene. The PHF1 (PHD finger protein 1) gene, from 6p21, is known to be rearranged in ESS in a promiscuous way inasmuch as it has been shown to recombine with JAZF1, EPC1, MEAF6, and now also with BRD8, in tumors of this type. In all rearrangements of PHF1, including the present one, a recurrent theme is that the entire coding part of PHF1 constitutes the 3' end of the fusion...
July 30, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28754964/enhancer-of-zeste-homolog-2-ezh2-induces-epithelial-mesenchymal-transition-in-endometriosis
#18
Qi Zhang, Peixin Dong, Xishi Liu, Noriaki Sakuragi, Sun-Wei Guo
EZH2, a subunit of the polycomb repressive complex 2 (PRC2) catalyzing trimethylation of histone H3 lysine 27 (H3K27), induces epithelial-mesenchymal transition (EMT) in cancers. However, whether EZH2 regulates EMT in endometriosis is unclear. Here, we show that EZH2 expression, along with its associated PRC2 proteins, is significantly elevated in ectopic and eutopic endometrium from women with endometriosis as compared with control endometrium. EZH2 knockdown or inhibition restored the epithelial phenotypes of endometriotic epithelial cells, concomitant with the upregulation of E-cadherin and downregulation of vimentin and transcription factors (Snail and Slug) as well as reduced cellular migratory and invasive propensity...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28754713/ubap2l-is-amplified-in-a-large-subset-of-human-lung-adenocarcinoma-and-is-critical-for-epithelial-lung-cell-identity-and-tumor-metastasis
#19
Romain Aucagne, Simon Girard, Nadine Mayotte, Bernhard Lehnertz, Stéphane Lopes-Paciencia, Patrick Gendron, Geneviève Boucher, Jalila Chagraoui, Guy Sauvageau
The ubiquitin-associated protein 2-like (UBAP2L) gene remains poorly studied in human and mouse development. UBAP2L interacts with the Polycomb group protein B lymphoma Mo-MLV insertion region 1 homolog (BMI1) and determines the activity of mouse hematopoietic stem cells in vivo Here we show that loss of Ubap2l leads to disorganized respiratory epithelium of mutant neonates, which die of respiratory failure. We also show that UBAP2L overexpression leads to epithelial-mesenchymal transition-like phenotype in a non-small cell lung carcinoma (NSCLC) cell line...
July 28, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28752843/loss-of-h3k27-trimethylation-is-not-suitable-for-distinguishing-malignant-peripheral-nerve-sheath-tumor-from-melanoma-a-study-of-387-cases-including-mimicking-lesions
#20
Sophie Le Guellec, Nicolas Macagno, Valérie Velasco, Laurence Lamant, Marick Lae, Thomas Filleron, Nausicaa Malissen, Elisabeth Cassagnau, Philippe Terrier, Christine Chevreau, Dominique Ranchere-Vince, Jean-Michel Coindre
The diagnosis of malignant peripheral nerve sheath tumor remains challenging, especially in the sporadic setting. Malignant peripheral nerve sheath tumor is a rare malignancy, and owing to the lack of specific histological criteria, immunohistochemical and molecular diagnostic markers, several differential diagnoses must be considered, in particular melanoma. Recently, inactivation of the polycomb repressive complex 2 (PRC2), induced by inactivating mutations in two of its critical constituents SUZ12 and EED, was reported in a large subset of malignant peripheral nerve sheath tumors...
July 28, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
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