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Polycomb repressor

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https://www.readbyqxmd.com/read/27904674/bmi1-plays-an-important-role-in-dentin-and-mandible-homeostasis-by-maintaining-redox-balance
#1
Ying Yin, Xian Xue, Qian Wang, Ning Chen, Dengshun Miao
To explore whether polycomb repressor Bmi1 plays an important role in dentin and mandible development homeostasis by maintaining redox balance, 3-week-old Bmi1 gene knockout (Bmi1(-/-)) mice were treated with the antioxidant N-acetylcysteine (NAC) for 2 weeks in their drinking water and phenotypes of the tooth and mandibles were compared with vehicle-treated Bmi1(-/-) mice and wild-type mice by radiograph, histochemistry and immunohistochemistry. Alterations of oxidative stress, DNA damage, cell proliferation and cell cycle-related parameters were also examined in mandibles...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27898079/a-dna-element-that-remembers-winter
#2
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-acetylation
#3
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 ALL 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 demonstrated that MLL-AF4 binds to the BCL-2 gene and directly activates it through DOT1L recruitment and increased H3K79me2/3 levels. Here, we perform a detailed analysis of MLL-AF4 regulation of the entire BCL-2 family...
November 14, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27819666/a-cis-cold-memory-element-and-a-trans-epigenome-reader-mediate-polycomb-silencing-of-flc-by-vernalization-in-arabidopsis
#4
Wenya Yuan, Xiao Luo, Zicong Li, Wannian Yang, Yizhong Wang, Rui Liu, Jiamu Du, Yuehui He
Some plants acquire competence to flower in spring after experiencing a seasonal temperature drop-winter cold, in a process termed vernalization. In Arabidopsis thaliana, prolonged exposure to cold induces epigenetic silencing of the potent floral repressor locus FLOWERING LOCUS C (FLC) by Polycomb group (PcG) proteins, and this silencing is stably maintained in subsequent growth and development upon return to warm temperatures. Here we show that a cis-regulatory DNA element in the nucleation region for PcG silencing at FLC and two homologous trans-acting epigenome readers, VAL1 and VAL2, control vernalization-mediated FLC silencing...
November 7, 2016: Nature Genetics
https://www.readbyqxmd.com/read/27716060/mir-27b-shapes-the-presynaptic-transcriptome-and-influences-neurotransmission-by-silencing-the-polycomb-group-protein-bmi1
#5
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
#6
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/27703144/bmi1-marks-distinct-castration-resistant-luminal-progenitor-cells-competent-for-prostate-regeneration-and-tumour-initiation
#7
Young A Yoo, Meejeon Roh, Anum F Naseem, Barbara Lysy, Mohamed M Desouki, Kenji Unno, Sarki A Abdulkadir
Identification of defined cell populations with stem/progenitor properties is key for understanding prostate development and tumorigenesis. Here we show that the polycomb repressor protein Bmi1 marks a population of castration-resistant luminal epithelial cells enriched in the mouse proximal prostate. We employ lineage tracing to show that these castration-resistant Bmi1-expressing cells (or CARBs) are capable of tissue regeneration and self-renewal. Notably, CARBs are distinct from the previously described luminal castration-resistant Nkx3...
October 5, 2016: Nature Communications
https://www.readbyqxmd.com/read/27659991/in-vivo-models-to-address-the-function-of-polycomb-group-proteins
#8
Frédéric Bantignies
Initially discovered as repressors of homeotic gene expression in Drosophila, Polycomb group (PcG) proteins have now been shown to be involved in a plethora of biological processes. Indeed, by repressing a large number of target genes, including specific lineage genes, these chromatin factors play major roles in a multitude of cellular functions, such as pluripotency, differentiation, reprogramming, tissue regeneration, and nuclear organization. In this book chapter are presented in vivo approaches and technologies, which have been used in both mammalian and Drosophila systems to study the cellular functions of Polycomb group proteins...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27659984/determination-of-polycomb-group-of-protein-compartmentalization-through-chromatin-fractionation-procedure
#9
Federica Marasca, Fabrizia Marullo, Chiara Lanzuolo
Epigenetic mechanisms modulate and maintain the transcriptional state of the genome acting at various levels on chromatin. Emerging findings suggest that the position in the nuclear space and the cross talk between components of the nuclear architecture play a role in the regulation of epigenetic signatures. We recently described a cross talk between the Polycomb group of proteins (PcG) epigenetic repressors and the nuclear lamina. This interplay is important for the maintenance of transcriptional repression at muscle-specific genes and for the correct timing of muscle differentiation...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27659971/chromatin-immunoprecipitation
#10
Laura Wiehle, Achim Breiling
Chromatin immunoprecipitation (ChIP) is a valuable method to investigate protein-DNA interactions in vivo. Since its discovery it has been indispensable to identify binding sites and patterns of a variety of DNA-interacting proteins, such as transcription factors and regulators, modified histones, and epigenetic modifiers. The Polycomb repressors were the first proteins that have been mapped using this technique, which provided the mechanistic basis for the understanding of their biological function. Cross-linked (XChIP) or native (NChIP) chromatin from tissues or cultured cells is fragmented and the protein of interest is immunoprecipitated using a specific antibody...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27651832/fine-tuning-of-chromatin-composition-and-polycomb-recruitment-by-two-mi2-homologues-during-c-elegans-early-embryonic-development
#11
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
#12
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/27614332/genome-wide-identification-evolution-of-chromobox-family-genes-and-their-expression-in-nile-tilapia
#13
Xing-Yong Liu, Xian-Bo Zhang, Ming-Hui Li, Shu-Qing Zheng, Zhi-Long Liu, Yun-Ying Cheng, De-Shou Wang
Chromobox (Cbx) family proteins are transcriptional repressors that involved in epigenetic and developmental processes. In this study, comprehensive analyses of Cbxs were performed using available genome databases from representative animal species. The Cbx family were originated from one Polycomb (Pc) gene like the yeast Pc, which duplicated into two and gave rise to the Pc and the Heterochromatin protein 1 (Hp1) identified in invertebrates from protozoon to lancelet. Rapid expansion of Cbx family members was observed in vertebrates as ~8 (5 Pc and 3 Hp1) were identified in spotted gar, coelacanth and tetrapods...
September 7, 2016: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/27581385/polycomb-and-trithorax-opposition-in-development-and-disease
#14
Steven T Poynter, Cigall Kadoch
Early discoveries in chromatin biology and epigenetics heralded new insights into organismal development. From these studies, two mediators of cellular differentiation were discovered: the Polycomb group (PcG) of transcriptional repressors, and the trithorax group (trxG) of transcriptional activators. These protein families, while opposed in function, work together to coordinate the appropriate cellular developmental programs that allow for both embryonic stem cell self-renewal and differentiation. Recently, both the PcG and trxG chromatin modulators have been observed to be deregulated in a wide spectrum diseases including developmental disorders and cancer...
November 2016: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/27557709/interdependence-of-prc1-and-prc2-for-recruitment-to-polycomb-response-elements
#15
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/27533460/the-putative-tumor-suppressor-gene-epha7-is-a-novel-bmi-1-target
#16
Gaëlle Prost, Sebastian Braun, Falk Hertwig, Marcus Winkler, Lucas Jagemann, Sara Nolbrant, Isabelle V Leefa, Nils Offen, Kenichi Miharada, Stefan Lang, Isabella Artner, Ulrike A Nuber
Bmi1 was originally identified as a gene that contributes to the development of mouse lymphoma by inhibiting MYC-induced apoptosis through repression of Ink4a and Arf. It codes for the Polycomb group protein BMI-1 and acts primarily as a transcriptional repressor via chromatin modifications. Although it binds to a large number of genomic regions, the direct BMI-1 target genes described so far do not explain the full spectrum of BMI-1-mediated effects. Here we identify the putative tumor suppressor gene EphA7 as a novel direct BMI-1 target in neural cells and lymphocytes...
August 13, 2016: Oncotarget
https://www.readbyqxmd.com/read/27498878/the-transcriptional-repressor-polycomb-group-factor-6-pcgf6-negatively-regulates-dendritic-cell-activation-and-promotes-quiescence
#17
Giselle M Boukhaled, Brendan Cordeiro, Genevieve Deblois, Vassil Dimitrov, Swneke D Bailey, Thomas Holowka, Anisa Domi, Hannah Guak, Huai-Hsuan Clare Chiu, Bart Everts, Edward J Pearce, Mathieu Lupien, John H White, Connie M Krawczyk
Pro-inflammatory signals provided by the microenvironment are critical to activate dendritic cells (DCs), components of the innate immune system that shape both innate and adaptive immunity. However, to prevent inappropriate immune activation, mechanisms must be in place to restrain DC activation to ensure DCs are activated only once sufficient stimuli have been received. Here, we report that DC activation and immunogenicity are regulated by the transcriptional repressor Polycomb group factor 6 (PCGF6). Pcgf6 is rapidly downregulated upon stimulation, and this downregulation is necessary to permit full DC activation...
August 16, 2016: Cell Reports
https://www.readbyqxmd.com/read/27471304/arabidopsis-transcriptional-repressor-val1-triggers-polycomb-silencing-at-flc-during-vernalization
#18
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
#19
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
https://www.readbyqxmd.com/read/27452518/the-snail-repressor-recruits-ezh2-to-specific-genomic-sites-through-the-enrollment-of-the-lncrna-hotair-in-epithelial-to-mesenchymal-transition
#20
C Battistelli, C Cicchini, L Santangelo, A Tramontano, L Grassi, F J Gonzalez, V de Nonno, G Grassi, L Amicone, M Tripodi
The transcription factor Snail is a master regulator of cellular identity and epithelial-to-mesenchymal transition (EMT) directly repressing a broad repertoire of epithelial genes. How chromatin modifiers instrumental to its activity are recruited to Snail-specific binding sites is unclear. Here we report that the long non-coding RNA (lncRNA) HOTAIR (for HOX Transcript Antisense Intergenic RNA) mediates a physical interaction between Snail and enhancer of zeste homolog 2 (EZH2), an enzymatic subunit of the polycomb-repressive complex 2 and the main writer of chromatin-repressive marks...
July 25, 2016: Oncogene
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