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Polycomb repressor

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https://www.readbyqxmd.com/read/28512107/divergent-requirements-for-ezh1-in-heart-development-versus-regeneration
#1
Shanshan Ai, Xianhong Yu, Yumei Li, Yong Peng, Chen Li, Yanzhu Yue, Ge Tao, Chuan-Yun Li, William T Pu, Aibin He
Rationale: Polycomb repressive complex 2 (PRC2) is a major epigenetic repressor that deposits methylation on histone H3 on lysine 27 (H3K27me) and controls differentiation and function of many cells, including cardiac myocytes. EZH1 and EZH2 are two alternative catalytic subunits with partial functional redundancy. The relative roles of EZH1 and EZH2 in heart development and regeneration are unknown. Objective: We compared the roles of EZH1 versus EZH2 in heart development and neonatal heart regeneration. Methods and Results: Heart development was normal in Ezh1(-/-) (E1KO) and Ezh2(f/f)::cTNT(-Cre) (E2KO) embryos...
May 16, 2017: Circulation Research
https://www.readbyqxmd.com/read/28455403/concerted-divergence-after-gene-duplication-in-polycomb-repressor-complexes
#2
Yichun Qiu, Shao-Lun Liu, Keith L Adams
Duplicated genes are a major contributor to genome evolution and phenotypic novelty. There are multiple possible evolutionary fates of duplicated genes. Here we provide an example of concerted divergence of simultaneously duplicated genes whose products function in the same complex. We studied PRC2 (Polycomb Repressive Complex 2) in Brassicaceae. The VRN-PRC2 complex contains VRN2 and SWN, and both genes were duplicated during a whole genome duplication to generate FIS2 and MEA which function in the Brassicaceae-specific FIS-PRC2 complex that regulates seed development...
April 28, 2017: Plant Physiology
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
#3
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)...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416772/dna-methylation-of-mettl7a-gene-body-regulates-its-transcriptional-level-in-thyroid-cancer
#4
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
#5
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/28410242/functional-and-therapeutic-significance-of-ezh2-in-urological-cancers
#6
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/28359242/small-molecule-inhibitors-of-epigenetic-mutations-as-compelling-drug-targets-for-myelodysplastic-syndromes
#7
Bani Bandana Ganguly
BACKGROUND: Involvement of mutations in epigenetic mechanism in development of heterogeneous MDS and its evolution to AML has been understood with at least one mutation and median of 2-3 mutations of the landscapes of driver mutations in ~40 genes described >90% MDS patients. Exclusivity and cooperating effects of mutations have directed therapeutic implementation with hypomethylating agents and identified a number of first-in-class small molecules as inhibitors of mutational expression...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28340355/the-human-immunodeficiency-virus-1-asp-rna-promotes-viral-latency-by-recruiting-the-polycomb-repressor-complex-2-and-promoting-nucleosome-assembly
#8
Juan C Zapata, Federica Campilongo, Robert A Barclay, Catherine DeMarino, Maria D Iglesias-Ussel, Fatah Kashanchi, Fabio Romerio
Various epigenetic marks at the HIV-1 5'LTR suppress proviral expression and promote latency. Cellular antisense transcripts known as long noncoding RNAs (lncRNAs) recruit the polycomb repressor complex 2 (PRC2) to gene promoters, which catalyzes trimethylation of lysine 27 on histone H3 (H3K27me3), thus promoting nucleosome assembly and suppressing gene expression. We found that an HIV-1 antisense transcript expressed from the 3'LTR and encoding the antisense protein ASP promotes proviral latency. Expression of ASP RNA reduced HIV-1 replication in Jurkat cells...
June 2017: Virology
https://www.readbyqxmd.com/read/28323035/naturally-occurring-anti-cancer-agents-targeting-ezh2
#9
Fahimeh Shahabipour, Michele Caraglia, Muhammed Majeed, Giuseppe Derosa, Pamela Maffioli, Amirhossein Sahebkar
Natural products are considered as promising tools for the prevention and treatment of cancer. The enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase unit of polycomb repressor complexes such as PRC2 complex that has oncogenic roles through interference with growth and metastatic potential. Several agents targeting EZH2 has been discovered but they often induce side effects in clinical trials. Recently, EZH2 has emerged as a potential target of natural products with documented anti-cancer effects and this discloses a new scenario for the development of EZH2 inhibitory strategies with agents with low cytotoxic detrimental effects...
March 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28320739/a-covalently-bound-inhibitor-triggers-ezh2-degradation-through-chip-mediated-ubiquitination
#10
Xu Wang, Wei Cao, Jianjun Zhang, Ming Yan, Qin Xu, Xiangbing Wu, Lixin Wan, Zhiyuan Zhang, Chenping Zhang, Xing Qin, Meng Xiao, Dongxia Ye, Yuyang Liu, Zeguang Han, Shaomeng Wang, Li Mao, Wenyi Wei, Wantao Chen
Enhancer of zeste homolog 2 (EZH2) has been characterized as a critical oncogene and a promising drug target in human malignant tumors. The current EZH2 inhibitors strongly suppress the enhanced enzymatic function of mutant EZH2 in some lymphomas. However, the recent identification of a PRC2- and methyltransferase-independent role of EZH2 indicates that a complete suppression of all oncogenic functions of EZH2 is needed. Here, we report a unique EZH2-targeting strategy by identifying a gambogenic acid (GNA) derivative as a novel agent that specifically and covalently bound to Cys668 within the EZH2-SET domain, triggering EZH2 degradation through COOH terminus of Hsp70-interacting protein (CHIP)-mediated ubiquitination...
May 2, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28157500/a-finer-print-than-tads-prc1-mediated-domains
#11
Elena Torlai Triglia, Tiago Rito, Ana Pombo
Polycomb proteins are well-known epigenetic repressors with unexplained roles in chromatin folding. In this issue of Molecular Cell, Kundu et al. (2017) investigate the structures of PRC1-mediated domains in stem cells and probe their changes upon differentiation and in PRC knockouts.
February 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28132848/vernalization-triggered-intragenic-chromatin-loop-formation-by-long-noncoding-rnas
#12
Dong-Hwan Kim, Sibum Sung
Long noncoding RNAs (lncRNAs) affect gene regulation through structural and regulatory interactions with associated proteins. The Polycomb complex often binds to lncRNAs in eukaryotes, and an lncRNA, COLDAIR, associates with Polycomb to mediate silencing of the floral repressor FLOWERING LOCUS C (FLC) during the process of vernalization in Arabidopsis. Here, we identified an additional Polycomb-binding lncRNA, COLDWRAP. COLDWRAP is derived from the repressed promoter of FLC and is necessary for the establishment of the stable repressed state of FLC by vernalization...
February 6, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28104398/down-regulation-of-boris-ctcfl-efficiently-regulates-cancer-stemness-and-metastasis-in-mycn-amplified-neuroblastoma-cell-line-by-modulating-wnt-%C3%AE-catenin-signaling-pathway
#13
Koteswara Rao Garikapati, Nibedita Patel, Venkata Krishna Kanth Makani, Priyanka Cilamkoti, Utpal Bhadra, Manika Pal Bhadra
BORIS/CTCFL is a vital nucleotide binding protein expressed during embryogenesis and gametogenesis. BORIS/CTCFL is the paralogue of transcriptional repressor protein CTCF, which is aberrantly expressed in various malignancies and primarily re-expressed in cancer stem cells (CSCs). The mechanism behind regulation of BORIS in various cancer conditions and tumor metastases is so far not explored in detail. The aim of the study was to understand the influence of BORIS/CTCFL on stemness and metastasis by regulating well-known oncogenes and related signaling pathways...
January 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28068325/trim28-interacts-with-ezh2-and-swi-snf-to-activate-genes-that-promote-mammosphere-formation
#14
J Li, Y Xi, W Li, R L McCarthy, S A Stratton, W Zou, W Li, S Y Dent, A K Jain, M C Barton
Histone methyl transferase EZH2 (Enhancer of Zeste Homolog 2) is generally associated with H3K27 methylation and gene silencing, as a member of the polycomb repressor 2 (PRC2) complex. Immunoprecipitation and mass spectrometry of the EZH2-protein interactome in estrogen receptor positive, breast cancer-derived MCF7 cells revealed EZH2 interactions with subunits of chromatin remodeler SWI/SNF complex and TRIM28, which formed a complex with EZH2 distinct from PRC2. Unexpectedly, transcriptome profiling showed that EZH2 primarily activates, rather than represses, transcription in MCF7 cells and with TRIM28 co-regulates a set of genes associated with stem cell maintenance and poor survival of breast cancer patients...
January 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28030829/cbx7-suppresses-cell-proliferation-migration-and-invasion-through-the-inhibition-of-pten-akt-signaling-in-pancreatic-cancer
#15
Sujie Ni, Hongwei Wang, Xiaolin Zhu, Chunhua Wan, Junfei Xu, Chen Lu, Li Xiao, Jiaqi He, Chongyi Jiang, Wei Wang, Zhixian He
Chromobox protein homolog 7 (CBX7), one of the polycomb group (PcG) proteins, is a transcriptional repressor involved in the regulation of cell proliferation and senescence. In the present study, we showed that CBX7 negatively regulates the proliferation, viability, chemoresistance, and migration of pancreatic cancer cells. Overexpression of CBX7 significantly inhibited the proliferation of pancreatic cancer cells in vitro and in vivo. Depletion of CBX7 facilitated their growth. CBX7 also impaired the viability and chemoresistance of pancreatic cancer cells...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/27984719/easy-stress-relief-by-ezh2
#16
Supriya G Prasanth, Kannanganattu V Prasanth
While we are beginning to appreciate the cellular roles played by long noncoding RNAs, the function of transcripts emerging from repetitive genomic regions remains enigmatic. In this issue, Zovoilis et al. report that the polycomb protein EZH2, upon heat shock, facilitates transcription of stress-responsive genes by inducing the degradation of the transcriptional repressor B2 repeat RNA.
December 15, 2016: Cell
https://www.readbyqxmd.com/read/27932267/human-pre-pik3c2b-an-intronic-cis-element-with-dual-function-of-activation-and-repression
#17
Jayant Maini, Mohsen Ghasemi, Deepti Yandhuri, Suman S Thakur, Vani Brahmachari
The Polycomb/Trithorax Responsive Elements (PRE/TREs) are the cis-regulatory sequences that interact with both repressive (PcG) as well as activating (TrxG) complexes. However, most of the mammalian PREs are demonstrated to interact with the repressive polycomb (PcG) complexes only. We have carried out an unbiased search for proteins interacting with human PRE-PIK3C2B (hPRE-PIK3C2B) based on DNA affinity purification followed by mass spectrometry and identified MLL, MLL4 and WDR87 among other proteins in three biological replicates in HEK, U87 and HeLa cell lines...
December 6, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27904674/bmi1-plays-an-important-role-in-dentin-and-mandible-homeostasis-by-maintaining-redox-balance
#18
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
#19
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%C3%A2-acetylation
#20
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 acute lymphoblastic leukemia 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 found that MLL-AF4 binds to the BCL-2 gene and directly activates it through DOT1L recruitment and increased H3K79me2/3 levels. In the study described here, we performed a detailed analysis of MLL-AF4 regulation of the entire BCL-2 family...
March 2017: Experimental Hematology
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