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Super-enhancer

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https://www.readbyqxmd.com/read/29053954/spt6-gets-in-the-way-of-polycomb-to-promote-esc-pluripotency
#1
François Robert
Despite expressing high levels of Polycomb group proteins, embryonic stem cells (ESCs) are refractory to H3K27 trimethylation, notably at super-enhancers regulating key pluripotency genes. In this issue of Molecular Cell, Wang et al. (2017) report that the histone chaperone Spt6 prevents H3K27 trimethylation of key ESC super-enhancers.
October 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29044238/addendum-guidance-of-regulatory-t-cell-development-by-satb1-dependent-super-enhancer-establishment
#2
Yohko Kitagawa, Naganari Ohkura, Yujiro Kidani, Alexis Vandenbon, Keiji Hirota, Ryoji Kawakami, Keiko Yasuda, Daisuke Motooka, Shota Nakamura, Motonari Kondo, Ichiro Taniuchi, Terumi Kohwi-Shigematsu, Shimon Sakaguchi
This corrects the article DOI: 10.1038/ni.3646.
October 18, 2017: Nature Immunology
https://www.readbyqxmd.com/read/29033324/the-elongation-factor-spt6-maintains-esc-pluripotency-by-controlling-super-enhancers-and-counteracting-polycomb-proteins
#3
A Hongjun Wang, Aster H Juan, Kyung Dae Ko, Pei-Fang Tsai, Hossein Zare, Stefania Dell'Orso, Vittorio Sartorelli
Spt6 coordinates nucleosome dis- and re-assembly, transcriptional elongation, and mRNA processing. Here, we report that depleting Spt6 in embryonic stem cells (ESCs) reduced expression of pluripotency factors, increased expression of cell-lineage-affiliated developmental regulators, and induced cell morphological and biochemical changes indicative of ESC differentiation. Selective downregulation of pluripotency factors upon Spt6 depletion may be mechanistically explained by its enrichment at ESC super-enhancers, where Spt6 controls histone H3K27 acetylation and methylation and super-enhancer RNA transcription...
October 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29026218/igd-class-switch-recombination-is-not-controlled-through-the-immunoglobulin-heavy-chain-3-regulatory-region-super-enhancer
#4
Hussein Issaoui, Nour Ghazzaui, Alexis Saintamand, Yves Denizot, François Boyer
No abstract text is available yet for this article.
October 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29024646/the-epstein-barr-virus-regulome-in-lymphoblastoid-cells
#5
Sizun Jiang, Hufeng Zhou, Jun Liang, Catherine Gerdt, Chong Wang, Liangru Ke, Stefanie C S Schmidt, Yohei Narita, Yijie Ma, Shuangqi Wang, Tyler Colson, Benjamin Gewurz, Guoliang Li, Elliott Kieff, Bo Zhao
Epstein-Barr virus (EBV) transforms B cells to continuously proliferating lymphoblastoid cell lines (LCLs), which represent an experimental model for EBV-associated cancers. EBV nuclear antigens (EBNAs) and LMP1 are EBV transcriptional regulators that are essential for LCL establishment, proliferation, and survival. Starting with the 3D genome organization map of LCL, we constructed a comprehensive EBV regulome encompassing 1,992 viral/cellular genes and enhancers. Approximately 30% of genes essential for LCL growth were linked to EBV enhancers...
October 11, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28991225/super-enhancers-define-a-proliferative-pgc-1%C3%AE-expressing-melanoma-subgroup-sensitive-to-bet-inhibition
#6
K A Gelato, L Schöckel, O Klingbeil, T Rückert, R Lesche, J Toedling, E Kalfon, M Héroult, P Lejeune, U Mönning, A E Fernández-Montalván, S Bäurle, S Siegel, B Haendler
Metabolic changes are linked to epigenetic reprogramming and play important roles in several tumor types. PGC-1α is a transcriptional coactivator controlling mitochondrial biogenesis and is linked to oxidative phosphorylation. We provide evidence that melanoma models with elevated PGC-1α levels are characteristic of the proliferative phenotype and are sensitive to bromodomain and extra-terminal domain (BET) inhibitor treatment. A super-enhancer region highly occupied by the BET family member BRD4 was identified for the PGC-1α gene...
October 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28990584/the-igh-3-regulatory-region-super-enhancer-does-not-control-iga-class-switch-recombination-in-the-b1-lineage
#7
Hussein Issaoui, Nour Ghazzaui, Alexis Saintamand, Claire Carrion, Christelle Oblet, Yves Denizot
No abstract text is available yet for this article.
October 9, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28980882/super-enhancers-new-analyses-and-perspectives-on-the-low-hanging-fruit
#8
Feda H Hamdan, Steven A Johnsen
Significant attention has recently been given to a class of enhancers termed "super enhancers", while implying that "typical enhancers" are less important. In this report, we examine criteria for identification of super enhancers and address the need to evaluate the differences between BRD4-occupied "typical" and "super" enhancers.
October 5, 2017: Transcription
https://www.readbyqxmd.com/read/28978570/enhancer-profiling-identifies-critical-cancer-genes-and-characterizes-cell-identity-in-adult-t-cell-leukemia
#9
Regina Wan Ju Wong, Phuong Cao Thi Ngoc, Wei Zhong Leong, Alice Wei Yee Yam, Tinghu Zhang, Kaori Asamitsu, Shinsuke Iida, Takashi Okamoto, Ryuzo Ueda, Nathanael S Gray, Takashi Ishida, Takaomi Sanda
A number of studies have recently demonstrated that "super-enhancers", which are large cluster of enhancers typically marked by a high level of acetylation of histone H3 lysine 27 and mediator bindings, are frequently associated with genes that control and define cell identity during normal development. Super-enhancers are also often enriched at cancer genes in various malignancies. Identification of such enhancers would pinpoint critical factors that directly contribute to pathogenesis. Here, we performed enhancer profiling using primary leukemia samples from adult T-cell leukemia/lymphoma (ATL), which is a genetically heterogeneous intractable cancer...
October 4, 2017: Blood
https://www.readbyqxmd.com/read/28977473/dbcorc-a-database-of-core-transcriptional-regulatory-circuitries-modeled-by-h3k27ac-chip-seq-signals
#10
Moli Huang, Ye Chen, Manqiu Yang, Anyuan Guo, Ying Xu, Liang Xu, H Phillip Koeffler
Core transcription regulatory circuitry (CRC) is comprised of a small group of self-regulated transcription factors (TFs) and their interconnected regulatory loops. Studies from embryonic stem cells and other cellular models have revealed the elementary roles of CRCs in transcriptional control of cell identity and cellular fate. Systematic identification and subsequent archiving of CRCs across diverse cell types and tissues are needed to explore both cell/tissue type-specific and disease-associated transcriptional networks...
September 5, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28974544/tert-structural-rearrangements-in-metastatic-pheochromocytomas
#11
Trisha Dwight, Aidan Flynn, Kaushalya Amarasinghe, Diana E Benn, Richard Lupat, Jason Li, Daniel Cameron, Annette Hogg, Shiva Balachander, Ida Lm Candiloro, Stephen Wong, Bruce G Robinson, Anthony T Papenfuss, Anthony J Gill, Alexander Dobrovic, Rodney J Hicks, Roderick Clifton-Bligh, Richard William Tothill
Pheochromocytomas (PC) and paragangliomas (PGL) are endocrine tumors for which the genetic and clinico-pathological features of metastatic progression remain incompletely understood. As a result, the risk of metastasis from a primary tumor cannot be predicted. Early diagnosis of individuals at high risk of developing metastases is clinically important and the identification of new biomarkers that are predictive of metastatic potential is of high value. Activation of TERT has been associated with a number of malignant tumors, including PC/PGL...
October 3, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28973462/analysis-of-primary-microrna-loci-from-nascent-transcriptomes-reveals-regulatory-domains-governed-by-chromatin-architecture
#12
Maria Bouvy-Liivrand, Ana Hernández de Sande, Petri Pölönen, Juha Mehtonen, Tapio Vuorenmaa, Henri Niskanen, Lasse Sinkkonen, Minna Unelma Kaikkonen, Merja Heinäniemi
Changes in mature microRNA (miRNA) levels that occur downstream of signaling cascades play an important role during human development and disease. However, the regulation of primary microRNA (pri-miRNA) genes remains to be dissected in detail. To address this, we followed a data-driven approach and developed a transcript identification, validation and quantification pipeline for characterizing the regulatory domains of pri-miRNAs. Integration of 92 nascent transcriptomes and multilevel data from cells arising from ecto-, endo- and mesoderm lineages reveals cell type-specific expression patterns, allows fine-resolution mapping of transcription start sites (TSS) and identification of candidate regulatory regions...
September 29, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28972897/simultaneous-adsorption-of-aflatoxin-b1-and-zearalenone-by-mono-and-di-alkyl-cationic-surfactants-modified-montmorillonites
#13
Gaofeng Wang, Yushan Miao, Zhiming Sun, Shuilin Zheng
Organo-montmorillonites (OMts) modified with mono- and di-alkyl cationic surfactants were prepared to remove polar mycotoxin aflatoxin B1 (AFB1) and weak polar, hydrophobic mycotoxin zearalenone (ZER) simultaneously. The structural and surface properties of the prepared OMts were investigated. In vitro adsorption experiments were carried out to simulate the in vivo conditions of gastrointestinal tract of animals by a batch mode. The adsorption of AFB1 and ZER in both single and binary-contaminate systems were investigated systematically...
September 25, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28971975/tbx4-is-involved-in-the-super-enhancer-driven-transcriptional-programs-underlying-features-specific-to-lung-fibroblasts
#14
Masafumi Horie, Naoya Miyashita, Yu Mikami, Satoshi Noguchi, Yasuhiro Yamauchi, Maho Suzukawa, Takeshi Fukami, Ken Ohta, Yoshihide Asano, Shinichi Sato, Yoko Yamaguchi, Mitsuhiro Ohshima, Hiroshi Suzuki, Akira Saito, Takahide Nagase
Lung fibroblasts participate in the pathogenesis of respiratory diseases, including lung cancer and pulmonary fibrosis. Although fibroblasts are ubiquitous constituents of various organs, their cellular diversity among different organs has been poorly characterized. Here, we aimed to investigate the distinct gene signature of lung fibroblasts that represents its pulmonary origin, and the underlying gene regulatory networks. Promoter-level differential expression analysis by cap analysis of gene expression (CAGE) sequencing revealed distinct gene expression patterns of fibroblasts derived from different anatomical sites and identified 88 coding genes with higher expression in lung fibroblasts relative to other fibroblasts...
September 28, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28963353/somatic-super-enhancer-duplications-and-hotspot-mutations-lead-to-oncogenic-activation-of-the-klf5-transcription-factor
#15
Xiaoyang Zhang, Peter S Choi, Joshua M Francis, Galen F Gao, Joshua D Campbell, Aruna Ramachandran, Yoichiro Mitsuishi, Gavin Ha, Juliann Shih, Francisca Vazquez, Aviad Tsherniak, Alison M Taylor, Jin Zhou, Zhong Wu, Ashton C Berger, Marios Giannakis, William C Hahn, Andrew D Cherniack, Matthew Meyerson
The Krüppel-like family of transcription factors (KLF) plays critical roles in human development and is associated with cancer pathogenesis. KLF5 has been shown to promote cancer cell proliferation and tumorigenesis, and to be genomically amplified in cancer cells. We recently reported that the KLF5 gene is also subject to other types of somatic coding and noncoding genomic alterations in diverse cancer types. Here we show that these alterations activate KLF5 by three distinct mechanisms. 1) Focal amplification of super-enhancers activates KLF5 expression in squamous cell carcinomas...
September 29, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28951465/super-enhancers-promote-transcriptional-dysregulation-in-nasopharyngeal-carcinoma
#16
Jiang Yuan, Yan-Yi Jiang, Anand Mayakonda, Moli Huang, Ling-Wen Ding, Han Lin, Fenggang Yu, Yanan Lu, Thomas Kwok Seng Loh, Marilynn Chow, Samantha L Savage, Jeffrey W Tyner, De-Chen Lin, H Phillip Koeffler
Nasopharyngeal carcinoma (NPC) is an invasive cancer with particularly high incidence in Southeast Asia and Southern China. The pathogenic mechanisms of NPC, particularly those involving epigenetic dysregulation, remain largely elusive, hampering clinical management of this malignancy. To identify novel druggable targets, we carried out an unbiased high-throughput chemical screening and observed that NPC cells were highly sensitive to inhibitors of cyclin-dependent kinases (CDK), especially THZ1, a covalent inhibitor of CDK7...
September 26, 2017: Cancer Research
https://www.readbyqxmd.com/read/28941026/transcription-instability-in-high-risk-neuroblastoma-is-associated-with-a-global-perturbation-of-chromatin-domains
#17
Carlo Zanon, Gian Paolo Tonini
Chromosome instability has a pivotal role among the hallmarks of cancer, but its transcriptional counterpart is rarely considered a relevant factor in cell destabilization. To examine transcription instability (TIN), we first devised a metric we named TIN index and used it to evaluate TIN on a dataset containing more than 500 neuroblastoma samples. We found that metastatic tumors from high-risk (HR) patients are characterized by significantly different TIN index values compared to low/intermediate-risk patients...
September 22, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28922346/grid-seq-reveals-the-global-rna-chromatin-interactome
#18
Xiao Li, Bing Zhou, Liang Chen, Lan-Tao Gou, Hairi Li, Xiang-Dong Fu
Higher eukaryotic genomes are bound by a large number of coding and non-coding RNAs, but approaches to comprehensively map the identity and binding sites of these RNAs are lacking. Here we report a method to capture in situ global RNA interactions with DNA by deep sequencing (GRID-seq), which enables the comprehensive identification of the entire repertoire of chromatin-interacting RNAs and their respective binding sites. In human, mouse, and Drosophila cells, we detected a large set of tissue-specific coding and non-coding RNAs that are bound to active promoters and enhancers, especially super-enhancers...
October 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28916725/characterization-of-enhancers-and-the-role-of-the-transcription-factor-klf7-in-regulating-corneal-epithelial-differentiation
#19
Rachel Herndon Klein, William Hu, Ghaidaa Kashgari, Ziguang Lin, Tuyen Nguyen, Michael Doan, Bogi Andersen
During tissue development, transcription factors bind regulatory DNA regions called enhancers, often located at great distances from the genes they regulate, to control gene expression. The enhancer landscape during embryonic stem cell differentiation has been well characterized. By contrast, little is known about the shared and unique enhancer regulatory mechanisms in different ectodermally derived epithelial cells. Here, we use ChIP-seq to identify domains enriched for histone marks H3K4me3, H3K4me1, and H3K27ac, and define for the first time the super enhancers and typical enhancers active in primary human corneal epithelial cells...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28910751/chromatin-reorganisation-in-epstein-barr-virus-infected-cells-and-its-role-in-cancer-development
#20
REVIEW
Michelle J West
The oncogenic Epstein-Barr virus (EBV) growth transforms B cells and drives lymphoma and carcinoma development. The virus encodes four key transcription factors (EBNA2, EBNA3A, EBNA3B and EBNA3C) that hijack host cell factors to bind gene control elements and reprogramme infected B cells. These viral factors predominantly target long-range enhancers to alter the expression of host cell genes that control B cell growth and survival and facilitate virus persistence. Enhancer and super-enhancer binding by these EBNAs results in large-scale reorganisation of three-dimensional enhancer-promoter architecture to drive the overexpression of oncogenes, the silencing of tumour suppressors and the modulation of transcription, cell-cycle progression, migration and adhesion...
September 11, 2017: Current Opinion in Virology
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