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Super enhancer transcription

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https://www.readbyqxmd.com/read/29907762/duplication-of-a-germline-promoter-downstream-of-the-igh-3-regulatory-region-impairs-class-switch-recombination
#1
Joana M Santos, Fatima-Zohra Braikia, Chloé Oudinet, Dania Haddad, Caroline Conte, Audrey Dauba, Ahmed Amine Khamlichi
During an adaptive immune response, B cells can change their surface immunoglobulins from IgM to IgG, IgE or IgA through a process called class switch recombination (CSR). Switching is preceded by inducible non-coding germline transcription (GLT) of the selected constant gene(s), which is largely controlled by a super-enhancer called the 3' regulatory region (3'RR). Despite intense efforts, the precise mechanisms that regulate GLT are still elusive. In order to gain additional insights into these mechanisms, we analyzed GLT and CSR in mutant B cells carrying a duplication of the promoter of the α constant gene (Iα) downstream of 3'RR...
June 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29904581/enhancer-functions-in-three-dimensions-beyond-the-flat-world-perspective
#2
REVIEW
Anita Göndör, Rolf Ohlsson
Transcriptional enhancers constitute a subclass of regulatory elements that facilitate transcription. Such regions are generally organized by short stretches of DNA enriched in transcription factor-binding sites but also can include very large regions containing clusters of enhancers, termed super-enhancers. These regions increase the probability or the rate (or both) of transcription generally in cis and sometimes over very long distances by altering chromatin states and the activity of Pol II machinery at promoters...
2018: F1000Research
https://www.readbyqxmd.com/read/29887316/palmitate-deranges-erythropoietin-production-via-transcription-factor-atf4-activation-of-unfolded-protein-response
#3
Thitinun Anusornvongchai, Masaomi Nangaku, Tzu-Ming Jao, Chia-Hsien Wu, Yu Ishimoto, Hiroshi Maekawa, Tetsuhiro Tanaka, Akira Shimizu, Masayuki Yamamoto, Norio Suzuki, Ryoji Sassa, Reiko Inagi
Lipotoxicity plays an important role in the progression of chronic kidney damage via various mechanisms, such as endoplasmic reticulum stress. Several studies proposed renal lipotoxicity in glomerular and tubular cells but the effect of lipid on renal erythropoietin (EPO)-producing (REP) cells in the interstitium has not been elucidated. Since renal anemia is caused by derangement of EPO production in REP cells, we evaluated the effect of palmitate, a representative long-chain saturated fatty acid, on EPO production and the endoplasmic reticulum stress pathway...
June 7, 2018: Kidney International
https://www.readbyqxmd.com/read/29884215/crebbp-ep300-bromodomains-are-critical-to-sustain-the-gata1-myc-regulatory-axis-in-proliferation
#4
Veronica Garcia-Carpizo, Sergio Ruiz-Llorente, Jacinto Sarmentero, Osvaldo Graña-Castro, David G Pisano, Maria J Barrero
BACKGROUND: The reported antitumor activity of the BET family bromodomain inhibitors has prompted the development of inhibitors against other bromodomains. However, the human genome encodes more than 60 different bromodomains and most of them remain unexplored. RESULTS: We report that the bromodomains of the histone acetyltransferases CREBBP/EP300 are critical to sustain the proliferation of human leukemia and lymphoma cell lines. EP300 is very abundant at super-enhancers in K562 and is coincident with sites of GATA1 and MYC occupancy...
June 8, 2018: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29777912/a-super-enhancer-maintains-homeostatic-expression-of-regnase-1
#5
Riyun Yang, Yuanyuan Wu, Yue Ming, Yuanpei Xu, Shouyan Wang, Jianbo Shen, Chenlu Wang, Xia Chen, Yongming Wang, Renfang Mao, Yihui Fan
Regnase-1 is not only a key component in maintaining intracellular homeostasis but also a critical negative regulator in preventing autoimmune diseases and cancer development. To keep homeostatic state, Regnase-1 has to be maintained at a desired level in multiple cell types. However, the molecular mechanism of keeping a certain transcriptional level of Reganase-1 is largely unknown. In this study, we found a super-enhancer (Reg-1-SE) around Regnase-1 gene is able to control the homeostatic expression of Regnase-1...
May 16, 2018: Gene
https://www.readbyqxmd.com/read/29771329/regulation-of-the-neuropathy-associated-pmp22-gene-by-a-distal-super-enhancer
#6
Harrison Pantera, John J Moran, Holly A Hung, Evgenia Pak, Amalia Dutra, John Svaren
Peripheral nerve myelination is adversely affected in the most common form of the hereditary peripheral neuropathy called Charcot-Marie-Tooth Disease. This form, classified as CMT1A, is caused by a 1.4 Mb duplication on chromosome 17, which includes the abundantly expressed Schwann cell myelin gene, Peripheral Myelin Protein 22 (PMP22). This is one of the most common copy number variants causing neurological disease. Overexpression of Pmp22 in rodent models recapitulates several aspects of neuropathy, and reduction of Pmp22 in such models results in amelioration of the neuropathy phenotype...
May 16, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29765516/selective-dissociation-between-lsd1-and-gfi1b-by-a-lsd1-inhibitor-ncd38-induces-the-activation-of-erg-super-enhancer-in-erythroleukemia-cells
#7
Ryusuke Yamamoto, Masahiro Kawahara, Shinji Ito, Junko Satoh, Goichi Tatsumi, Masakatsu Hishizawa, Takayoshi Suzuki, Akira Andoh
Lysine-specific demethylase 1 (LSD1) is a histone modifier for transcriptional repression involved in the regulation of hematopoiesis. We previously reported that a LSD1 inhibitor NCD38 induces transdifferentiation from erythroid lineage to granulomonocytic lineage and exerts anti-leukemia effect through de-repression of the specific super-enhancers of hematopoietic regulators including ERG in a human erythroleukemia cell line, HEL. However, the mechanistic basis for this specificity of NCD38 has remained unclear...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29760797/-lmo1-super-enhancer-polymorphism-rs2168101-g-t-correlates-with-decreased-neuroblastoma-risk-in-chinese-children
#8
Jing He, Xiaohong Zhang, Jiao Zhang, Ruizhong Zhang, Tianyou Yang, Jinhong Zhu, Huimin Xia, Yan Zou
Neuroblastoma is one of the most frequently occurring childhood cancers. The rs2168101 G>T polymorphism observed in the LMO1 gene is located at a conserved GATA transcription factor binding motif. This polymorphism was reported to be significantly associated with neuroblastoma susceptibility. However, whether this and other functional polymorphisms can affect neuroblastoma risk of Chinese children remains unknown. We conducted a two-center hospital-based case-control study with a total of 374 cases and 812 controls to assess the role of five LMO1 gene polymorphisms in the neuroblastoma risk...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29754476/targeting-super-enhancers-for-disease-treatment-and-diagnosis
#9
Ha Youn Shin
The transcriptional regulation of genes determines the fate of animal cell differentiation and subsequent organ development. With the recent progress in genome-wide technologies, the genomic landscapes of enhancers have been broadly explored in mammalian genomes, which led to the discovery of novel specific subsets of enhancers, termed superenhancers. Super-enhancers are large clusters of enhancers covering the long region of regulatory DNA and are densely occupied by transcription factors, active histone marks, and co-activators...
May 10, 2018: Molecules and Cells
https://www.readbyqxmd.com/read/29741610/aff4-promotes-tumorigenesis-and-tumor-initiation-capacity-of-head-and-neck-squamous-cell-carcinoma-cells-by-regulating-sox2
#10
Peng Deng, Jiongke Wang, Xuefeng Zhang, Xingyu Wu, Ning Ji, Jing Li, Min Zhou, Lu Jiang, Xin Zeng, Qianming Chen
Super elongation complex (SEC) controls gene transcription by releasing Pol II from pausing. Previous studies have shown that dysfunction of SEC was associated with multiple human cancers, such as leukemia and breast cancer. However, the role of SEC in head and neck squamous cell carcinoma (HNSCC) development remains largely unknown. In this study, we found expression of AF4/FMR2 family member 4 (AFF4), the core component of SEC, was upregulated dramatically in HNSCC cell lines and tumor tissues. By using siRNA-mediated depletion and overexpression of AFF4, we demonstrated AFF4 promoted proliferation, migration and invasion of HNSCC cells...
May 8, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29724031/targeting-general-transcriptional-machinery-as-a-therapeutic-strategy-for-adult-t-cell-leukemia
#11
REVIEW
Regina Wan Ju Wong, Takashi Ishida, Takaomi Sanda
Cancer cells are highly reliant on certain molecular pathways, which support their survival and proliferation. The fundamental concept of molecularly targeted therapy is to target a protein that is specifically deregulated or overexpressed in cancer cells. However, drug resistance and tumor heterogeneity are major obstacles in the development of specific inhibitors. Additionally, many driver oncogenes exert their oncogenic property via abnormal expression without having genetic mutations. Interestingly, recent accumulating evidence has demonstrated that many critical cancer genes are driven by a unique class of enhancers termed super-enhancers...
May 2, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29717274/detecting-epistasis-within-chromatin-regulatory-circuitry-reveals-cand2-as-a-novel-susceptibility-gene-for-obesity
#12
Shan-Shan Dong, Shi Yao, Yi-Xiao Chen, Yan Guo, Yu-Jie Zhang, Hui-Min Niu, Ruo-Han Hao, Hui Shen, Qing Tian, Hong-Wen Deng, Tie-Lin Yang
BACKGROUND: Genome-wide association studies have identified many susceptibility loci for obesity. However, missing heritability problem is still challenging and ignorance of genetic interactions is believed to be an important cause. Current methods for detecting interactions usually do not consider regulatory elements in non-coding regions. Interaction analyses within chromatin regulatory circuitry may identify new susceptibility loci. METHODS: We developed a pipeline named interaction analyses within chromatin regulatory circuitry (IACRC), to identify genetic interactions impacting body mass index (BMI)...
May 1, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29706548/the-energetics-and-physiological-impact-of-cohesin-extrusion
#13
Laura Vian, Aleksandra Pękowska, Suhas S P Rao, Kyong-Rim Kieffer-Kwon, Seolkyoung Jung, Laura Baranello, Su-Chen Huang, Laila El Khattabi, Marei Dose, Nathanael Pruett, Adrian L Sanborn, Andres Canela, Yaakov Maman, Anna Oksanen, Wolfgang Resch, Xingwang Li, Byoungkoo Lee, Alexander L Kovalchuk, Zhonghui Tang, Steevenson Nelson, Michele Di Pierro, Ryan R Cheng, Ido Machol, Brian Glenn St Hilaire, Neva C Durand, Muhammad S Shamim, Elena K Stamenova, José N Onuchic, Yijun Ruan, Andre Nussenzweig, David Levens, Erez Lieberman Aiden, Rafael Casellas
Cohesin extrusion is thought to play a central role in establishing the architecture of mammalian genomes. However, extrusion has not been visualized in vivo, and thus, its functional impact and energetics are unknown. Using ultra-deep Hi-C, we show that loop domains form by a process that requires cohesin ATPases. Once formed, however, loops and compartments are maintained for hours without energy input. Strikingly, without ATP, we observe the emergence of hundreds of CTCF-independent loops that link regulatory DNA...
May 17, 2018: Cell
https://www.readbyqxmd.com/read/29690904/ocean-c-mapping-hubs-of-open-chromatin-interactions-across-the-genome-reveals-gene-regulatory-networks
#14
Tingting Li, Lumeng Jia, Yong Cao, Qing Chen, Cheng Li
We develop a method called open chromatin enrichment and network Hi-C (OCEAN-C) for antibody-independent mapping of global open chromatin interactions. By integrating FAIRE-seq and Hi-C, OCEAN-C detects open chromatin interactions enriched by active cis-regulatory elements. We identify more than 10,000 hubs of open chromatin interactions (HOCIs) in human cells, which are mainly active promoters and enhancers bound by many DNA-binding proteins and form interaction networks crucial for gene transcription. In addition to identifying large-scale topological structures, including topologically associated domains and A/B compartments, OCEAN-C can detect HOCI-mediated chromatin interactions that are strongly associated with gene expression, super-enhancers, and broad H3K4me3 domains...
April 24, 2018: Genome Biology
https://www.readbyqxmd.com/read/29684085/the-kat5-acetyl-histone4-brd4-axis-silences-hiv-1-transcription-and-promotes-viral-latency
#15
Zichong Li, Uri Mbonye, Zeming Feng, Xiaohui Wang, Xiang Gao, Jonathan Karn, Qiang Zhou
The bromodomain protein Brd4 promotes HIV-1 latency by competitively inhibiting P-TEFb-mediated transcription induced by the virus-encoded Tat protein. Brd4 is recruited to the HIV LTR by interactions with acetyl-histones3 (AcH3) and AcH4. However, the precise modification pattern that it reads and the writer for generating this pattern are unknown. By examining a pool of latently infected proviruses with diverse integration sites, we found that the LTR characteristically has low AcH3 but high AcH4 content...
April 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29680705/over-expression-of-3-hydroxy-3-methylglutaryl-coenzyme-a-reductase-1-hmgr1-gene-under-super-promoter-for-enhanced-latex-biosynthesis-in-rubber-tree-hevea-brasiliensis-muell-arg
#16
R Jayashree, P A Nazeem, K Rekha, S Sreelatha, A Thulaseedharan, R Krishnakumar, R G Kala, M Vineetha, P Leda, U Jinu, P Venkatachalam
Natural rubber (cis-1, 4-polyisoprene) is being produced from bark laticifer cells of Hevea brasiliensis and the popular high latex yielding Indian rubber clones are easily prone to onset of tapping panel dryness syndrome (TPD) which is considered as a physiological syndrome affecting latex production either partially or completely. This report describes an efficient protocol for development of transgenic rubber plants by over-expression of 3-hydroxy 3-methylglutaryl Co-enzyme A reductase 1 (hmgr1) gene which is considered as rate limiting factor for latex biosynthesis via Agrobacterium-mediated transformation...
June 2018: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/29648668/widespread-enhancer-activation-via-er%C3%AE-mediates-estrogen-response-in-vivo-during-uterine-development
#17
Wendy N Jefferson, H Karimi Kinyamu, Tianyuan Wang, Adam X Miranda, Elizabeth Padilla-Banks, Alisa A Suen, Carmen J Williams
Little is known regarding how steroid hormone exposures impact the epigenetic landscape in a living organism. Here, we took a global approach to understanding how exposure to the estrogenic chemical, diethylstilbestrol (DES), affects the neonatal mouse uterine epigenome. Integration of RNA- and ChIP-sequencing data demonstrated that ∼80% of DES-altered genes had higher H3K4me1/H3K27ac signal in close proximity. Active enhancers, of which ∼3% were super-enhancers, had a high density of estrogen receptor alpha (ERα) binding sites and were correlated with alterations in nearby gene expression...
April 10, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29644114/super-enhancer-inhibitors-suppress-myc-driven-transcriptional-amplification-and-tumor-progression-in-osteosarcoma
#18
Demeng Chen, Zhiqiang Zhao, Zixin Huang, Du-Chu Chen, Xin-Xing Zhu, Yi-Ze Wang, Ya-Wei Yan, Shaojun Tang, Subha Madhavan, Weiyi Ni, Zhan-Peng Huang, Wen Li, Weidong Ji, Huangxuan Shen, Shuibin Lin, Yi-Zhou Jiang
Osteosarcoma is the most common primary bone sarcoma that mostly occurs in young adults. The causes of osteosarcoma are heterogeneous and still not fully understood. Identification of novel, important oncogenic factors in osteosarcoma and development of better, effective therapeutic approaches are in urgent need for better treatment of osteosarcoma patients. In this study, we uncovered that the oncogene MYC is significantly upregulated in metastastic osteosarcoma samples. In addition, high MYC expression is associated with poor survival of osteosarcoma patients...
2018: Bone Research
https://www.readbyqxmd.com/read/29625024/a-common-type-2-diabetes-risk-variant-potentiates-activity-of-an-evolutionarily-conserved-islet-stretch-enhancer-and-increases-c2cd4a-and-c2cd4b-expression
#19
Ina Kycia, Brooke N Wolford, Jeroen R Huyghe, Christian Fuchsberger, Swarooparani Vadlamudi, Romy Kursawe, Ryan P Welch, Ricardo d'Oliveira Albanus, Asli Uyar, Shubham Khetan, Nathan Lawlor, Mohan Bolisetty, Anubhuti Mathur, Johanna Kuusisto, Markku Laakso, Duygu Ucar, Karen L Mohlke, Michael Boehnke, Francis S Collins, Stephen C J Parker, Michael L Stitzel
Genome-wide association studies (GWASs) and functional genomics approaches implicate enhancer disruption in islet dysfunction and type 2 diabetes (T2D) risk. We applied genetic fine-mapping and functional (epi)genomic approaches to a T2D- and proinsulin-associated 15q22.2 locus to identify a most likely causal variant, determine its direction of effect, and elucidate plausible target genes. Fine-mapping and conditional analyses of proinsulin levels of 8,635 non-diabetic individuals from the METSIM study support a single association signal represented by a cluster of 16 strongly associated (p < 10-17 ) variants in high linkage disequilibrium (r2 > 0...
April 5, 2018: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29577113/stat1-is-required-for-suppression-of-type-17-immunity-during-influenza-and-bacterial-superinfection
#20
Benjamin Lee, Radha Gopal, Michelle L Manni, Kevin J McHugh, Sivanarayana Mandalapu, Keven M Robinson, John F Alcorn
Influenza is an annual, global health care concern. Secondary bacterial pneumonia is a severe complication associated with primary influenza virus infection, often resulting in critical morbidity and mortality. Our laboratory has identified influenza-induced suppression of anti-bacterial Type 17 immunity as a mechanism for enhanced susceptibility to bacterial super-infection. We have shown that influenza-induced type I interferon impairs Type 17 activation. STAT1 is a transcription factor involved in interferon signaling, shared by type I, II, and III interferon...
August 1, 2017: ImmunoHorizons
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