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Super enhancer transcription

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https://www.readbyqxmd.com/read/29196865/parent-perceptions-of-psychosocial-outcomes-of-equine-assisted-interventions-for-children-with-autism-spectrum-disorder
#1
Vanessa Xue-Ling Tan, Janette Graetz Simmonds
This research explored parents' perceptions of the psychosocial outcomes of their children's experience of receiving equine-assisted interventions (EAI). Participants were the parents of six children (aged 3-14) diagnosed with autism spectrum disorder. Five semi-structured interviews were conducted and the transcript data was analysed using Interpretative phenomenological analysis. Four super-ordinate themes emerged from the analysis: (1) child's improved self-concept and enhanced emotional well-being, (2) child's improved self-regulatory ability, (3) social benefits for the child, and (4) unexpected outcomes...
December 1, 2017: Journal of Autism and Developmental Disorders
https://www.readbyqxmd.com/read/29196127/lncrnas-and-circrnas-from-the-same-gene-masterpieces-of-rna-splicing
#2
Ma-Sha Huang, Tao Zhu, Ling Li, Pan Xie, Xi Li, Hong-Hao Zhou, Zhao-Qian Liu
Accumulating evidence has shown that lncRNAs and circRNAs are novel regulators of gene expression. The discovery of numerous lncRNAs and circRNAs, and investigation into their structures and functions will contribute to our understanding of the pathogenesis of diseases as well as better prevention, diagnosis, and treatment of diseases. There is a close relationship between circRNAs and lncRNAs regarding to their origins and functions. Recent studies have shown that non-coding linear and circular transcripts can be transcribed from the same gene and are potential super-enhancers modulating gene transcription...
November 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29149598/harnessing-bet-inhibitor-sensitivity-reveals-amigo2-as-a-melanoma-survival-gene
#3
Barbara Fontanals-Cirera, Dan Hasson, Chiara Vardabasso, Raffaella Di Micco, Praveen Agrawal, Asif Chowdhury, Madeleine Gantz, Ana de Pablos-Aragoneses, Ari Morgenstern, Pamela Wu, Dan Filipescu, David Valle-Garcia, Farbod Darvishian, Jae-Seok Roe, Michael A Davies, Christopher R Vakoc, Eva Hernando, Emily Bernstein
Bromodomain and extraterminal domain inhibitors (BETi) represent promising therapeutic agents for metastatic melanoma, yet their mechanism of action remains unclear. Here we interrogated the transcriptional effects of BETi and identified AMIGO2, a transmembrane molecule, as a BET target gene essential for melanoma cell survival. AMIGO2 is upregulated in melanoma cells and tissues compared to human melanocytes and nevi, and AMIGO2 silencing in melanoma cells induces G1/S arrest followed by apoptosis. We identified the pseudokinase PTK7 as an AMIGO2 interactor whose function is regulated by AMIGO2...
November 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29133788/regulation-of-angiotensin-ii-actions-by-enhancers-and-super-enhancers-in-vascular-smooth-muscle-cells
#4
Sadhan Das, Parijat Senapati, Zhuo Chen, Marpadga A Reddy, Rituparna Ganguly, Linda Lanting, Varun Mandi, Anita Bansal, Amy Leung, Selena Zhang, Ye Jia, Xiwei Wu, Dustin E Schones, Rama Natarajan
Angiotensin II (AngII) promotes hypertension and atherosclerosis by activating growth-promoting and pro-inflammatory gene expression in vascular smooth muscle cells (VSMCs). Enhancers and super-enhancers (SEs) play critical roles in driving disease-associated gene expression. However, enhancers/SEs mediating VSMC dysfunction remain uncharacterized. Here, we show that AngII alters vascular enhancer and SE repertoires in cultured VSMCs in vitro, ex vivo, and in AngII-infused mice aortas in vivo. AngII-induced enhancers/SEs are enriched in binding sites for signal-dependent transcription factors and dependent on key signaling kinases...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29129929/il-2-imprints-human-naive-b-cell-fate-towards-plasma-cell-through-erk-elk1-mediated-bach2-repression
#5
Nicolas Hipp, Hannah Symington, Cédric Pastoret, Gersende Caron, Céline Monvoisin, Karin Tarte, Thierry Fest, Céline Delaloy
Plasma cell differentiation is a tightly regulated process that requires appropriate T cell helps to reach the induction threshold. To further understand mechanisms by which T cell inputs regulate B cell fate decision, we investigate the minimal IL-2 stimulation for triggering human plasma cell differentiation in vitro. Here we show that the timed repression of BACH2 through IL-2-mediated ERK/ELK1 signalling pathway directs plasma cell lineage commitment. Enforced BACH2 repression in activated B cells unlocks the plasma cell transcriptional program and induces their differentiation into immunoglobulin M-secreting cells...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29102610/systematic-analysis-of-the-determinants-of-gene-expression-noise-in-embryonic-stem-cells
#6
Andre J Faure, Jörn M Schmiedel, Ben Lehner
Isogenic cells in a common environment show substantial cell-to-cell variation in gene expression, often referred to as "expression noise." Here, we use multiple single-cell RNA-sequencing datasets to identify features associated with high or low expression noise in mouse embryonic stem cells. These include the core promoter architecture of a gene, with CpG island promoters and a TATA box associated with low and high noise, respectively. High noise is also associated with "conflicting" chromatin states-the absence of transcription-associated histone modifications or the presence of repressive ones in active genes...
November 22, 2017: Cell Systems
https://www.readbyqxmd.com/read/29092931/cistrome-cancer-a-web-resource-for-integrative-gene-regulation-modeling-in-cancer
#7
Shenglin Mei, Clifford A Meyer, Rongbin Zheng, Qian Qin, Qiu Wu, Peng Jiang, Bo Li, Xiaohui Shi, Binbin Wang, Jingyu Fan, Celina Shih, Myles Brown, Chongzhi Zang, X Shirley Liu
Cancer results from a breakdown of normal gene expression control, so the study of gene regulation is critical to cancer research. To gain insight into the transcriptional and epigenetic factors regulating abnormal gene expression patterns in cancers, we developed the Cistrome Cancer web resource (http://cistrome.org/CistromeCancer/). We conducted the systematic integration and modeling of over 10,000 tumor molecular profiles from The Cancer Genome Atlas (TCGA) with over 23,000 ChIP-seq and chromatin accessibility profiles from our Cistrome collection...
November 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/29033324/the-elongation-factor-spt6-maintains-esc-pluripotency-by-controlling-super-enhancers-and-counteracting-polycomb-proteins
#8
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/29024646/the-epstein-barr-virus-regulome-in-lymphoblastoid-cells
#9
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/29017057/a-p53-super-tumor-suppressor-reveals-a-tumor-suppressive-p53-ptpn14-yap-axis-in-pancreatic-cancer
#10
Stephano S Mello, Liz J Valente, Nitin Raj, Jose A Seoane, Brittany M Flowers, Jacob McClendon, Kathryn T Bieging-Rolett, Jonghyeob Lee, Danton Ivanochko, Margaret M Kozak, Daniel T Chang, Teri A Longacre, Albert C Koong, Cheryl H Arrowsmith, Seung K Kim, Hannes Vogel, Laura D Wood, Ralph H Hruban, Christina Curtis, Laura D Attardi
The p53 transcription factor is a critical barrier to pancreatic cancer progression. To unravel mechanisms of p53-mediated tumor suppression, which have remained elusive, we analyzed pancreatic cancer development in mice expressing p53 transcriptional activation domain (TAD) mutants. Surprisingly, the p53(53,54) TAD2 mutant behaves as a "super-tumor suppressor," with an enhanced capacity to both suppress pancreatic cancer and transactivate select p53 target genes, including Ptpn14. Ptpn14 encodes a negative regulator of the Yap oncoprotein and is necessary and sufficient for pancreatic cancer suppression, like p53...
October 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28991225/super-enhancers-define-a-proliferative-pgc-1%C3%AE-expressing-melanoma-subgroup-sensitive-to-bet-inhibition
#11
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/28977473/dbcorc-a-database-of-core-transcriptional-regulatory-circuitries-modeled-by-h3k27ac-chip-seq-signals
#12
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/28973462/analysis-of-primary-microrna-loci-from-nascent-transcriptomes-reveals-regulatory-domains-governed-by-chromatin-architecture
#13
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/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 I 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/28955517/aff1-and-aff4-differentially-regulate-the-osteogenic-differentiation-of-human-mscs
#16
Chen-Chen Zhou, Qiu-Chan Xiong, Xin-Xing Zhu, Wen Du, Peng Deng, Xiao-Bing Li, Yi-Zhou Jiang, Shu-Juan Zou, Cun-Yu Wang, Quan Yuan
AFF1 and AFF4 belong to the AFF (AF4/FMR2) family of proteins, which function as scaffolding proteins linking two different transcription elongation factors, positive elongation factor b (P-TEFb) and ELL1/2, in super elongation complexes (SECs). Both AFF1 and AFF4 regulate gene transcription through elongation and chromatin remodeling. However, their function in the osteogenic differentiation of mesenchymal stem cells (MSCs) is unknown. In this study, we show that small interfering RNA (siRNA)-mediated depletion of AFF1 in human MSCs leads to increased alkaline phosphatase (ALP) activity, enhanced mineralization and upregulated expression of osteogenic-related genes...
2017: Bone Research
https://www.readbyqxmd.com/read/28951465/super-enhancers-promote-transcriptional-dysregulation-in-nasopharyngeal-carcinoma
#17
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
#18
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...
November 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28922346/grid-seq-reveals-the-global-rna-chromatin-interactome
#19
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
#20
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
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