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https://www.readbyqxmd.com/read/29772549/long-non-coding-rna-and-polycomb-an-intricate-partnership-in-cancer-biology
#1
Cyrinne Achour, Francesca Aguilo
High-throughput analyses have revealed that the vast majority of the transcriptome does not code for proteins. These non-translated transcripts, when larger than 200 nucleotides, are termed long non-coding RNAs (lncRNAs), and play fundamental roles in diverse cellular processes. LncRNAs are subject to dynamic chemical modification, adding another layer of complexity to our understanding of the potential roles that lncRNAs play in health and disease. Many lncRNAs regulate transcriptional programs by influencing the epigenetic state through direct interactions with chromatin-modifying proteins...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29765032/pcgf5-is-required-for-neural-differentiation-of-embryonic-stem-cells
#2
Mingze Yao, Xueke Zhou, Jiajian Zhou, Shixin Gong, Gongcheng Hu, Jiao Li, Kaimeng Huang, Ping Lai, Guang Shi, Andrew P Hutchins, Hao Sun, Huating Wang, Hongjie Yao
Polycomb repressive complex 1 (PRC1) is an important regulator of gene expression and development. PRC1 contains the E3 ligases RING1A/B, which monoubiquitinate lysine 119 at histone H2A (H2AK119ub1), and has been sub-classified into six major complexes based on the presence of a PCGF subunit. Here, we report that PCGF5, one of six PCGF paralogs, is an important requirement in the differentiation of mouse embryonic stem cells (mESCs) towards a neural cell fate. Although PCGF5 is not required for mESC self-renewal, its loss blocks mESC neural differentiation by activating the SMAD2/TGF-β signaling pathway...
May 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29764119/founder-mutations-for-early-onset-melanoma-as-revealed-by-whole-exome-sequencing-suggests-that-this-is-not-associated-with-the-increasing-incidence-of-melanoma-in-poland
#3
Tadeusz Dębniak, Rodney J Scott, Rodney A Lea, Bohdan Górski, Bartłomiej Masojć, Cezary Cybulski, Andrzej Kram, Romuald Maleszka, Tomasz Gromowski, Katarzyna Paszkowska-Szczur, Aniruddh Kashyap, Marcin R Lener, Karolina Malińska, Emilia Rogoża, Dawid Murawa, Helena Rudnicka, Jakub Deptuła, Jan Lubiński
Purpose: Germline mutations within melanoma susceptibility genes are present only in minority of melanoma patients and it is expected that additional genes will be discovered with next generation sequence technology and whole-exome sequencing. Material and Methods: Herein we performed whole-exome sequencing (WES) on a cohort of 96 unrelated Polish patients with melanoma diagnosed under the age of 40 years who all screened negative for the presence of CDKN2A-variants...
May 14, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29752448/regulation-of-proliferation-and-cell-cycle-by-protein-regulator-of-cytokinesis-1-in-oral-squamous-cell-carcinoma
#4
Fanglong Wu, Xueke Shi, Rui Zhang, Yuan Tian, Xiangjian Wang, Changlei Wei, Duo Li, Xiaoyu Li, Xiangli Kong, Yurong Liu, Weihua Guo, Yiqing Guo, Hongmei Zhou
Protein regulator of cytokinesis 1 (PRC1), a microtubule-associated protein, has emerged as a critical regulator of proliferation and apoptosis, acting predominantly in numerous tumors. However, its function in oral squamous cell carcinoma (OSCC) is still unknown. To establish the roles of PRC1 in OSCC, 95 oral clinical samples (54 OSCC, 24 oral leukoplakia [OLK], and 17 normal oral mucosa) and seven oral cell lines (6 OSCC and 1 normal oral cell lines) were analyzed using a series of molecular and genomic assays both in vivo and in vitro were conducted in this study...
May 11, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29748662/reducing-protein-regulator-of-cytokinesis-1-as-a-prospective-therapy-for-hepatocellular-carcinoma
#5
Xinran Liu, Yangkai Li, Lijing Meng, Xin-Yuan Liu, Anlin Peng, Yuchen Chen, Chengyu Liu, Hong Chen, Sheng Sun, Xiaoping Miao, Yu Zhang, Ling Zheng, Kun Huang
Proteins that bind to microtubule are important for cell cycle, and some of these proteins show oncogenic characteristics with mechanisms not fully understood. Herein we demonstrate overexpression of protein regulator of cytokinesis 1 (PRC1), a microtubule-associated regulator of mitosis, in human hepatocellular carcinoma (HCC). Moreover, upregulated PRC1 is associated with lower survival rates of HCC patients. Mechanistically, reducing PRC1 blocks mitotic exit of HCC cells at telophase in a spindle assembly checkpoint independent manner, and acts synergistically with microtubule-associated agents (MTAs) to suppress p53-wt or p53-null HCC cells in a p53- or p14ARF-dependent manner; while overexpressing PRC1 increases the resistance of HCC to taxol...
May 10, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29727681/prc1-fine-tunes-gene-repression-and-activation-to-safeguard-skin-development-and-stem-cell-specification
#6
Idan Cohen, Dejian Zhao, Carmit Bar, Victor J Valdes, Katherine L Dauber-Decker, Minh Binh Nguyen, Manabu Nakayama, Michael Rendl, Wendy A Bickmore, Haruhiko Koseki, Deyou Zheng, Elena Ezhkova
Polycomb repressive complexes (PRCs) 1 and 2 are essential chromatin regulators of cell identity. PRC1, a dominant executer of Polycomb-mediated control, functions as multiple sub-complexes that possess catalytic-dependent H2AK119 mono-ubiquitination (H2AK119ub) and catalytic-independent activities. Here, we show that, despite its well-established repressor functions, PRC1 binds to both silent and active genes. Through in vivo loss-of-function studies, we show that global PRC1 function is essential for skin development and stem cell (SC) specification, whereas PRC1 catalytic activity is dispensable...
May 3, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29723807/the-molecular-selectivity-of-unc3866-inhibitor-for-polycomb-cbx7-protein-from-molecular-dynamics-simulation
#7
Hui Liu, Zhuoming Li, Lang Li
Polycomb CBX proteins regulate gene expression by targeting Polycomb repressive complex 1 (PRC1) to sites of H3K27me3 via their chromodomains, which plays a key role in the development of numerous cancers. UNC3866, is a recently reported peptide-based inhibitor of the methyllysine (Kme) reading function of CBX chromodomains (CBX2, 4 and 6-8). The previous experiments showed that UNC3866 bound the chromodomains of CBX7 strongly, with ∼20-fold selectivity over other CBX chromodomains. However, the potential mechanism of UNC3866 preferentially binding to CBX7 is still unknown...
April 10, 2018: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29721964/the-evaluation-of-bmi1-posttranslational-modifications-during-retinal-degeneration-to-understand-bmi1-action-on-photoreceptor-death-execution
#8
Martial K Mbefo, Yvan Arsenijevic
Retinitis Pigmentosa (RP) is a class of hereditary retinal dystrophy associated with gradual visual failure and a subsequent loss of light-sensitive cells in the retina, leading to blindness. Many mutated genes were found to be causative of this disease. Despite a number of compiling efforts, the process of cell death in photoreceptors remains to be clearly elucidated. We recently reported an abnormal cell cycle reentry in photoreceptors undergoing degeneration in Rd1 mice, a model of RP, and identified the polycomb repressive complex 1 (PRC1) core component BMI1 as a critical molecular factor orchestrating the cell death mechanism...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29670361/identification-of-molecular-target-genes-and-key-pathways-in-hepatocellular-carcinoma-by-bioinformatics-analysis
#9
Lei Zhou, Yanyan Du, Lingqun Kong, Xingyuan Zhang, Qiangpu Chen
Background and aim: Hepatocellular carcinoma (HCC) is a major cause of cancer mortality and is increasing incidence worldwide. The aim of this study was to identify the key genes and microRNAs in HCC and explore their potential mechanisms. Methods: The gene expression profiles of GSE76427, GSE64041, GSE57957, and the microRNA dataset GSE67882 were downloaded from the Gene Expression Omnibus database. The online tool GEO2R was used to obtain differentially expressed genes (DEGs) and miRNAs (DEMs)...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29667247/the-nuclear-factor-constans-complex-antagonizes-polycomb-repression-to-de-repress-flowering-locus-t-expression-in-response-to-inductive-long-days-in-arabidopsis
#10
Xiao Luo, Zheng Gao, Yizhong Wang, Zhijuan Chen, Wenju Zhang, Jirong Huang, Hao Yu, Yuehui He
Many plants sense the seasonal cues, day length or photoperiod changes, to align the timing of the developmental transition to flowering with changing seasons for reproductive success. Inductive day lengths through the photoperiod pathway induces the expression of FLOWERING LOCUS T (FT) or FT relatives that encode a major mobile florigen to promote flowering. In Arabidopsis thaliana, under inductive long days the photoperiod pathway output CONSTANS (CO) accumulates toward the end of the day and associates with the B and C subunits of Nuclear Factor Y (NF-Y) to form the NF-CO complex that acts to promote FT expression near dusk, whereas Polycomb group (PcG) proteins function to silence FT expression...
April 18, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29661849/feedback-regulation-by-antagonistic-epigenetic-factors-potentially-maintains-homeostasis-in-drosophila
#11
Devendran A Sadasivam, Der-Hwa Huang
Polycomb group (PcG) repressors confer epigenetically heritable silencing on key regulatory genes through histone H3 trimethylation on lysine 27 (H3K27me3). How the silencing state withstands antagonistic activities from co-expressed trithorax group (trxG) activators is unclear. Using overexpression of Trx H3K4 methylase to perturb the silenced state, we find a dynamic process triggered in a stepwise fashion to neutralize the inductive impacts from excess Trx. Shortly after Trx overexpression, there are global increases in H3K4 trimethylation and RNA polymerase II phosphorylation, marking active transcription...
April 16, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29606589/the-h3k36me2-methyltransferase-nsd1-demarcates-prc2-mediated-h3k27me2-and-h3k27me3-domains-in-embryonic-stem-cells
#12
Gundula Streubel, Ariane Watson, Sri Ganesh Jammula, Andrea Scelfo, Darren J Fitzpatrick, Giorgio Oliviero, Rachel McCole, Eric Conway, Eleanor Glancy, Gian Luca Negri, Eugene Dillon, Kieran Wynne, Diego Pasini, Nevan J Krogan, Adrian P Bracken, Gerard Cagney
The Polycomb repressor complex 2 (PRC2) is composed of the core subunits Ezh1/2, Suz12, and Eed, and it mediates all di- and tri-methylation of histone H3 at lysine 27 in higher eukaryotes. However, little is known about how the catalytic activity of PRC2 is regulated to demarcate H3K27me2 and H3K27me3 domains across the genome. To address this, we mapped the endogenous interactomes of Ezh2 and Suz12 in embryonic stem cells (ESCs), and we combined this with a functional screen for H3K27 methylation marks. We found that Nsd1-mediated H3K36me2 co-locates with H3K27me2, and its loss leads to genome-wide expansion of H3K27me3...
April 19, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29563611/hipk2-and-extrachromosomal-histone-h2b-are-separately-recruited-by-aurora-b-for-cytokinesis
#13
Laura Monteonofrio, Davide Valente, Manuela Ferrara, Serena Camerini, Roberta Miscione, Marco Crescenzi, Cinzia Rinaldo, Silvia Soddu
Cytokinesis, the final phase of cell division, is necessary to form two distinct daughter cells with correct distribution of genomic and cytoplasmic materials. Its failure provokes genetically unstable states, such as tetraploidization and polyploidization, which can contribute to tumorigenesis. Aurora-B kinase controls multiple cytokinetic events, from chromosome condensation to abscission when the midbody is severed. We have previously shown that HIPK2, a kinase involved in DNA damage response and development, localizes at the midbody and contributes to abscission by phosphorylating extrachromosomal histone H2B at Ser14...
March 22, 2018: Oncogene
https://www.readbyqxmd.com/read/29539429/combinatorial-control-of-recruitment-of-a-variant-prc1-6-complex-in-embryonic-stem-cells
#14
Yikai Huang, Wukui Zhao, Congcong Wang, Yaru Zhu, Mengjie Liu, Huan Tong, Yin Xia, Qing Jiang, Jinzhong Qin
Though genetic data suggest that Polycomb group proteins (PcGs) are central chromatin modifiers and repressors that have been implicated in control of embryonic stem cell (ESC) pluripotency, the precise mechanism of PcG complex recruitment remains elusive, especially in mammals. We now report that the first and second MBT repeats of L3mbtl2 are important structural and functional features that are necessary and sufficient for L3mbtl2-mediated recruitment of PRC1.6 complex to target promoters. Interestingly, this region of L3mbtl2 harbors the evolutionarily conserved Pho-binding pocket also present in Drosophila Sfmbt, and mutation of the critical residues within this pocket completely abolishes its interaction with target promoters...
March 13, 2018: Cell Reports
https://www.readbyqxmd.com/read/29528145/timosaponin-a-iii-inhibits-oncogenic-phenotype-via-regulation-of-pcg-protein-bmi1-in-breast-cancer-cells
#15
Joseph E Gergely, Armond E Dorsey, Goberdhan P Dimri, Manjari Dimri
Polycomb group (PcG) protein BMI1 is an important regulator of oncogenic phenotype and is often overexpressed in several human malignancies including breast cancer. Aberrant expression of BMI1 is associated with metastasis and poor prognosis in cancer patients. At present, therapy reagents that can efficiently inhibit the expression of BMI1 are not very well known. Here, we report that Timosaponin A-III (TA-III), a steroidal saponin obtained from the rhizomes of an herb, Anemarrhena asphodeloides, strongly inhibits expression of BMI1 in breast cancer cells...
March 12, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29523508/ss18-ssx-induces-the-expression-of-neurogenic-genes-to-drive-synovial-sarcoma
#16
(no author information available yet)
SS18-SSX usurps the PRC1.1 repressive complex to drive expression of a synovial sarcoma gene signature.
May 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29514932/a-newly-characterized-vacuolar-serine-carboxypeptidase-atg42-ybr139w-is-required-for-normal-vacuole-function-and-the-terminal-steps-of-autophagy-in-the-yeast-saccharomyces-cerevisiae
#17
Katherine R Parzych, Aileen Ariosa, Muriel Mari, Daniel J Klionsky
Macroautophagy (hereafter autophagy) is a cellular recycling pathway essential for cell survival during nutrient deprivation that culminates in the degradation of cargo within the vacuole in yeast and the lysosome in mammals, followed by efflux of the resultant macromolecules back into the cytosol. The yeast vacuole is home to many different hydrolytic proteins and while few have established roles in autophagy, the involvement of others remains unclear. The vacuolar serine carboxypeptidase Y (Prc1) has not been previously shown to have a role in vacuolar zymogen activation and has not been directly implicated in the terminal degradation steps of autophagy...
May 1, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29514326/cellulose-synthase-mutants-distinctively-affect-cell-growth-and-cell-wall-integrity-for-plant-biomass-production-in-arabidopsis
#18
Huizhen Hu, Ran Zhang, Zhangsheng Tao, Xukai Li, Yuyang Li, Jiangfeng Huang, Xinxin Li, Xiao Han, Shengqiu Feng, Guimin Zhang, Liangcai Peng
Cellulose is the most characteristic component of plant cell walls and plays a central role in plant mechanical strength and morphogenesis. Despite cellulose synthase (CesA) mutants have exhibited a reduction of cellulose level, much remains unknown about their impacts on the cell growth (elongation and division) and cell wall integrity that fundamentally determine plant growth. Here, we examined three major types of AtCesAs mutants (rsw1, AtCesA1 mutant; prc1-1 and cesa6, AtCesA6-null mutants; IRX3, AtCesA7 mutant) and transgenic mutants that overexpressed AtCesAs genes in the background of AtCesA6-null mutants...
March 5, 2018: Plant & Cell Physiology
https://www.readbyqxmd.com/read/29513657/epigenetic-reprogramming-enables-the-transition-from-primordial-germ-cell-to-gonocyte
#19
Peter W S Hill, Harry G Leitch, Cristina E Requena, Zhiyi Sun, Rachel Amouroux, Monica Roman-Trufero, Malgorzata Borkowska, Jolyon Terragni, Romualdas Vaisvila, Sarah Linnett, Hakan Bagci, Gopuraja Dharmalingham, Vanja Haberle, Boris Lenhard, Yu Zheng, Sriharsa Pradhan, Petra Hajkova
Gametes are highly specialized cells that can give rise to the next generation through their ability to generate a totipotent zygote. In mice, germ cells are first specified in the developing embryo around embryonic day (E) 6.25 as primordial germ cells (PGCs). Following subsequent migration into the developing gonad, PGCs undergo a wave of extensive epigenetic reprogramming around E10.5-E11.5, including genome-wide loss of 5-methylcytosine. The underlying molecular mechanisms of this process have remained unclear, leading to our inability to recapitulate this step of germline development in vitro...
March 15, 2018: Nature
https://www.readbyqxmd.com/read/29502955/the-ss18-ssx-oncoprotein-hijacks-kdm2b-prc1-1-to-drive-synovial-sarcoma
#20
Ana Banito, Xiang Li, Aimée N Laporte, Jae-Seok Roe, Francisco Sanchez-Vega, Chun-Hao Huang, Amanda R Dancsok, Katerina Hatzi, Chi-Chao Chen, Darjus F Tschaharganeh, Rohit Chandwani, Nilgun Tasdemir, Kevin B Jones, Mario R Capecchi, Christopher R Vakoc, Nikolaus Schultz, Marc Ladanyi, Torsten O Nielsen, Scott W Lowe
Synovial sarcoma is an aggressive cancer invariably associated with a chromosomal translocation involving genes encoding the SWI-SNF complex component SS18 and an SSX (SSX1 or SSX2) transcriptional repressor. Using functional genomics, we identify KDM2B, a histone demethylase and component of a non-canonical polycomb repressive complex 1 (PRC1.1), as selectively required for sustaining synovial sarcoma cell transformation. SS18-SSX1 physically interacts with PRC1.1 and co-associates with SWI/SNF and KDM2B complexes on unmethylated CpG islands...
March 12, 2018: Cancer Cell
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