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https://www.readbyqxmd.com/read/28720707/intrinsically-disordered-chromatin-protein-nupr1-binds-to-the-c-terminal-region-of-polycomb-ring1b
#1
Patricia Santofimia-Castaño, Bruno Rizzuti, Ángel L Pey, Philippe Soubeyran, Miguel Vidal, Raúl Urrutia, Juan L Iovanna, José L Neira
Intrinsically disordered proteins (IDPs) are ubiquitous in eukaryotes, and they are often associated with diseases in humans. The protein NUPR1 is a multifunctional IDP involved in chromatin remodeling and in the development and progression of pancreatic cancer; however, the details of such functions are unknown. Polycomb proteins are involved in specific transcriptional cascades and gene silencing. One of the proteins of the Polycomb complex is the Ring finger protein 1 (RING1). RING1 is related to aggressive tumor features in multiple cancer types...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28717045/multitasking-by-polycomb-response-elements
#2
Elizabeth S Jaensch, Sharmistha Kundu, Robert E Kingston
Development requires the expression of master regulatory genes necessary to specify a cell lineage. Equally significant is the stable and heritable silencing of master regulators that would specify alternative lineages. This regulated gene silencing is carried out by Polycomb group (PcG) proteins, which must be correctly recruited only to the subset of their target loci that requires lineage-specific silencing. A recent study by Erceg and colleagues (pp. 590-602) expands on a key aspect of that targeting: The same DNA elements that recruit PcG complexes to a repressed locus also encode transcriptional enhancers that function in different lineages where that locus must be expressed...
June 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28714959/o-glcnacylation-modulates-bmi-1-protein-stability-and-potential-oncogenic-function-in-prostate-cancer
#3
Y Li, L Wang, J Liu, P Zhang, M An, C Han, Y Li, X Guan, K Zhang
The Polycomb group transcriptional repressor Bmi-1 often overexpressed and participated in stem cells self-renewal and tumorigenesis initiating of prostate cancer. In this progression, Bmi-1 protein was regulated by transcription and post-translational modifications (PTMs). Nobly, the underlying PTMs regulation of Bmi-1 is poorly known. Here we use co-immunoprecipitation show that in C4-2 cell line, Bmi-1 directly interacted with OGT which is the only known enzyme catalyzed the O-GlcNAcylation in human. Furthermore, we identified that Ser255 is the site for Bmi-1 O-GlcNAcylation, and O-GlcNAcylation promoted Bmi-1 protein stability and its oncogenic activity...
July 17, 2017: Oncogene
https://www.readbyqxmd.com/read/28712876/drosophila-sce-dring-e3-ligase-inhibits-apoptosis-in-a-dp53-dependent-manner
#4
Rocío Simón, Carolina J Simoes da Silva, Sol Fereres, Ana Busturia
The Polycomb group (PcG) of proteins control developmental gene silencing and are highly conserved between flies and mammals. PcG proteins function by controlling post-translational modification of histones, such as ubiquitylation, which impacts chromatin compaction and thus gene transcription. Changes in PcG cellular levels have drastic effects on organismal development and are involved in the generation of human pathologies such as cancer. However, the mechanisms controlling their levels of expression and their physiological effects are only partially understood...
July 13, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28711634/role-of-epigenetic-modulation-in-cancer-stem-cell-fate
#5
REVIEW
Abhijeet Deshmukh, Mudra Binju, Frank Arfuso, Philip Newsholme, Arun Dharmarajan
A sub-population of the tumor micro-environment consists of cancer stem cells (CSCs), which are responsible for the initiation and recurrence of cancer. Recently, epigenetic processes such as DNA methylation, histone modification, and chromatin remodelling have been found to be involved in inducing epigenetic factors in CSCs. Most of these processes, such as DNA methylation, generally occur in the genome that is rich in Cytosine-Guanine repeat sequences, also known as CpG islands, which are distributed throughout the human genome...
July 12, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28710118/correction-for-wang-et-al-comparative-analysis-of-chromatin-binding-by-sex-comb-on-midleg-scm-and-other-polycomb-group-repressors-at-a-drosophila-hox-gene
#6
Liangjun Wang, Neal Jahren, Ellen L Miller, Carrie S Ketel, Daniel R Mallin, Jeffrey A Simon
No abstract text is available yet for this article.
August 1, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28706074/germ-line-inherited-h3k27me3-restricts-enhancer-function-during-maternal-to-zygotic-transition
#7
Fides Zenk, Eva Loeser, Rosaria Schiavo, Fabian Kilpert, Ozren Bogdanović, Nicola Iovino
Gametes carry parental genetic material to the next generation. Stress-induced epigenetic changes in the germ line can be inherited and can have a profound impact on offspring development. However, the molecular mechanisms and consequences of transgenerational epigenetic inheritance are poorly understood. We found that Drosophila oocytes transmit the repressive histone mark H3K27me3 to their offspring. Maternal contribution of the histone methyltransferase Enhancer of zeste, the enzymatic component of Polycomb repressive complex 2, is required for active propagation of H3K27me3 during early embryogenesis...
July 14, 2017: Science
https://www.readbyqxmd.com/read/28700942/a-pml-slit-axis-controls-physiological-cell-migration-and-cancer-invasion-in-the-cns
#8
Valeria Amodeo, Deli A, Joanne Betts, Stefano Bartesaghi, Ying Zhang, Angela Richard-Londt, Matthew Ellis, Rozita Roshani, Mikaella Vouri, Sara Galavotti, Sarah Oberndorfer, Ana Paula Leite, Alan Mackay, Aikaterini Lampada, Eva Wessel Stratford, Ningning Li, David Dinsdale, David Grimwade, Chris Jones, Pierluigi Nicotera, David Michod, Sebastian Brandner, Paolo Salomoni
Cell migration through the brain parenchyma underpins neurogenesis and glioblastoma (GBM) development. Since GBM cells and neuroblasts use the same migratory routes, mechanisms underlying migration during neurogenesis and brain cancer pathogenesis may be similar. Here, we identify a common pathway controlling cell migration in normal and neoplastic cells in the CNS. The nuclear scaffold protein promyelocytic leukemia (PML), a regulator of forebrain development, promotes neural progenitor/stem cell (NPC) and neuroblast migration in the adult mouse brain...
July 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28698559/repression-of-abd-b-by-polycomb-is-critical-for-cell-identity-maintenance-in-adult-drosophila-testis
#9
Shuo Zhang, Chenyu Pan, Xiangdong Lv, Wei Wu, Hao Chen, Wenqing Wu, Hailong Wu, Lei Zhang, Yun Zhao
Hox genes play a fundamental role in regulating animal development. However, less is known about their functions on homeostasis maintenance in adult stem cells. Here, we report that the repression of an important axial Hox gene, Abdominal-B (Abd-B), in cyst stem cells (CySCs) is essential for the homeostasis and cell identity maintenance in the adult Drosophila testis. Derepression of Abd-B in CySCs disrupts the proper self-renewal of both germline stem cells (GSCs) and CySCs, and leads to an excessive expansion of early stage somatic cells, which originate from both lineages...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698395/long-noncoding-rna-xist-promotes-malignancies-of-esophageal-squamous-cell-carcinoma-via-regulation-of-mir-101-ezh2
#10
Xiaoliang Wu, Xiaoxiao Dinglin, Xing Wang, Wen Luo, Qi Shen, Yong Li, Ling Gu, Qianghua Zhou, Haotu Zhu, Yanjie Li, Chaodi Tan, Xianzi Yang, Zhenfeng Zhang
The long non-coding RNA XIST is a long non-coding RNA that associates with polycomb repressive complex 2 to regulate X-chromosome inactivation in female mammals. The biological roles as well as the underlying mechanisms of XIST in esophageal squamous cell carcinoma remained yet to be solved. Our data indicated that XIST was significantly upregulated in esophageal squamous cancerous tissues and cancer cell lines, as compared with that in the corresponding non-cancerous tissues and immortalized normal squamous epithelial cells...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28679998/deregulated-polycomb-complex-function-in-the-pathogenesis-of-mds
#11
Atsushi Iwama
Epigenetic regulation holds a key role in gene expression due to its modulation of the structure and function of chromatin. Notably, epigenetic dysregulation is deeply involved in the pathogenesis of hematological malignancies. Polycomb group (PcG) genes encoding histone modifier proteins are representative epigenetic genes that regulate a variety of cellular functions, including self-renewal and multi-lineage differentiation of stem cells. Surprisingly, many PcG genes are targeted by deletions or somatic mutations or both in a number of hematological malignancies, such as myelodysplastic syndrome (MDS)...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28679862/mysm1-2a-dub-is-an-epigenetic-regulator-in-human-melanoma-and-contributes-to-tumor-cell-growth
#12
Christina Wilms, Carsten M Kroeger, Adelheid V Hainzl, Ishani Banik, Clara Bruno, Ioanna Krikki, Vida Farsam, Meinhard Wlaschek, Martina V Gatzka
Histone modifying enzymes, such as histone deacetylases (HDACs) and polycomb repressive complex (PRC) components, have been implicated in regulating tumor growth, epithelial-mesenchymal transition, tumor stem cell maintenance, or repression of tumor suppressor genes - and may be promising targets for combination therapies of melanoma and other cancers. According to recent findings, the histone H2A deubiquitinase 2A-DUB/Mysm1 interacts with the p53-axis in hematopoiesis and tissue differentiation in mice, in part by modulating DNA-damage responses in stem cell and progenitor compartments...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28672805/epigenetic-regulation-of-the-epithelial-to-mesenchymal-transition-in-lung-cancer
#13
REVIEW
Joëlle Roche, Robert M Gemmill, Harry A Drabkin
Lung cancer is the leading cause of cancer deaths worldwide. It is an aggressive and devastating cancer because of metastasis triggered by enhanced migration and invasion, and resistance to cytotoxic chemotherapy. The epithelial to mesenchymal transition (EMT) is a fundamental developmental process that is reactivated in wound healing and a variety of diseases including cancer where it promotes migration/invasion and metastasis, resistance to treatment, and generation and maintenance of cancer stem cells. The induction of EMT is associated with reprogramming of the epigenome...
June 24, 2017: Cancers
https://www.readbyqxmd.com/read/28666925/ezh2-upregulation-correlates-with-tumor-invasiveness-proliferation-and-angiogenesis-in-human-pituitary-adenomas
#14
Bin Liu, Bo Pang, Qirui Wang, Shengji Yang, Taihong Gao, Qian Ding, Huajie Liu, Yihang Yang, Haitao Fan, Rui Zhang, Tao Xin, Guangming Xu, Qi Pang
Enhancer of zeste homolog 2 (EZH2) is a critical component of the polycomb repressive complex 2 (PRC2), which epigenetically represses genes involved in tumorigenesis and is highly expressed in tumors. However, no studies have investigated EZH2 expression and its clinical significance in human pituitary adenomas (PAs). Therefore, we examined the expression pattern of EZH2 in PAs and studied the correlations between protein expression and invasiveness, proliferation, angiogenesis, hormone functioning, and some other factors...
June 27, 2017: Human Pathology
https://www.readbyqxmd.com/read/28666321/androgens-regulate-ovarian-gene-expression-through-modulation-of-ezh2-expression-and-activity
#15
Xiaoting Ma, Emily Hayes, Anindita Biswas, Christina Seger, Hen Prizant, Stephen R Hammes, Aritro Sen
Significant evidence suggests that androgen signaling through classical androgen receptors is critical for both normal and pathologic ovarian physiology. Specifically, we and others have shown that, in mouse granulosa cells, androgen actions through both extra-nuclear and nuclear androgen receptor signaling are critical for normal follicle development and ovulation. Here we show that androgens through the PI3K/Akt pathway rapidly (within minutes) phosphorylate and inhibit activity of the Polycomb group protein enhancer of zeste homologue 2 (Ezh2)...
June 28, 2017: Endocrinology
https://www.readbyqxmd.com/read/28665982/the-sertad-protein-taranis-plays-a-role-in-polycomb-mediated-gene-repression
#16
Pranabananda Dutta, Willis X Li
The Polycomb group (PcG) proteins have been implicated in epigenetic transcriptional repression in development, stem cell maintenance and in cancer. The chromodomain protein Polycomb (Pc) is a key member of the PcG. Pc binds to the histone mark, trimethylated histone 3 lysine 27 (H3K27me3), to initiate transcriptional repression. How PcG proteins are recruited to target loci is not fully understood. Here we show that the Drosophila SERTA domain protein Taranis (Tara) is involved in transcriptional regulation of Pc target genes...
2017: PloS One
https://www.readbyqxmd.com/read/28665819/targeting-ezh2-in-cancer-therapy
#17
Makoto Yamagishi, Kaoru Uchimaru
PURPOSE OF REVIEW: The present review introduces recent outstanding progress pertaining to Enhancer of zeste homolog 2 (EZH2), especially regarding its mode of action as a master regulator of chromatin, and provides molecular-based evidence for targeting EZH2 in cancer therapy. We discuss the active development of small molecules targeting the enzymatic activity of EZH2/polycomb repressive complex 2 (PRC2). RECENT FINDINGS: Genetic, transcriptional, and posttranscriptional dysregulation of EZH2 is frequently observed in many cancer types...
July 13, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28664185/the-mir-125a-and-mir-320c-are-potential-tumor-suppressor-micrornas-epigenetically-silenced-by-the-polycomb-repressive-complex-2-in-multiple-myeloma
#18
Mohammad Alzrigat, Helena Jernberg-Wiklund
We have previously presented the histone methyltransferase enhancer of zeste homolog 2 (EZH2) of the polycomb repressive complex 2 (PRC2) as a potential therapeutic target in Multiple Myeloma (MM). In a recent article in Oncotarget by Alzrigat. et al. 2017, we have reported on the novel finding that EZH2 inhibition using the highly selective inhibitor of EZH2 enzymatic activity, UNC1999, reactivated the expression of microRNA genes previously reported to be underexpressed in MM. Among these, we have identified miR-125a-3p and miR-320c as potential tumor suppressor microRNAs as they were predicted to target MM-associated oncogenes; IRF-4, XBP-1 and BLIMP-1...
2017: RNA & Disease
https://www.readbyqxmd.com/read/28658556/epigenetic-regulation-of-t-helper-cell-differentiation-memory-and-plasticity-in-allergic-asthma
#19
REVIEW
Damon J Tumes, Magdalene Papadopoulos, Yusuke Endo, Atsushi Onodera, Kiyoshi Hirahara, Toshinori Nakayama
An estimated 300 million people currently suffer from asthma, which causes approximately 250 000 deaths a year. Allergen-specific T-helper (Th) cells produce cytokines that induce many of the hallmark features of asthma including airways hyperreactivity, eosinophilic and neutrophilic inflammation, mucus hypersecretion, and airway remodeling. Cytokine-producing Th subsets including Th1 (IFN-γ), Th2 (IL-4, IL-5, IL-13), Th9 (IL-9), Th17 (IL-17), Th22 (IL-22), and T regulatory (IL-10) cells have all been suggested to play a role in the development of asthma...
July 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28656062/c-myc-is-required-for-braf-v600e-induced-epigenetic-silencing-by-h3k27me3-in-tumorigenesis
#20
Yiping Qu, Qi Yang, Juan Liu, Bingyin Shi, Meiju Ji, Gang Li, Peng Hou
BRAF(V600E) mutation is frequently found in human cancers particularly thyroid cancer and melanoma, and is involved in the regulation of gene expression through activating MAPK/Erk signaling. Trimethylation of histone 3 lysine 27 (H3K27me3) is a critical epigenetic mark for the maintenance of gene silencing in tumorigenesis. However, molecular mechanism underlying the complex interplay between these two molecular events remains to be explored. In the present study, we conducted chromatin immunoprecipitation combined with next-generation sequencing (ChIP-Seq) and expression microarray analysis in NIH3T3 cells to explore the relationship between H3K27me3 and transcriptional regulation by BRAF(V600E) mutation...
2017: Theranostics
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