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Chromatin-associated RNA

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https://www.readbyqxmd.com/read/28426349/rna-binging-protein-rbm14-regulates-dissociation-and-association-of-non-homologous-end-joining-proteins
#1
Nicholas Simon, Ming Yuan, Mihoko Kai
Defects in DNA damage response (DDR) are associated with multiple diseases, including cancers and neurodegenerative disorders. Emerging evidence indicates involvement of RNA-binding proteins (RBPs) in DDR. However, functions of the RBPs in DDR pathways remain elusive. We have shown previously that the RNA-binding protein RBM14 is required for non-homologous end joining (NHEJ). Here we show that RBM14 is required for efficient recruitment of XRCC4 and XLF to chromatin and release of KU proteins from chromatin upon DNA damage...
April 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28423509/histone-lysine-methyltransferase-g9a-is-a-novel-epigenetic-target-for-the-treatment-of-hepatocellular-carcinoma
#2
Masayuki Yokoyama, Tetsuhiro Chiba, Yoh Zen, Motohiko Oshima, Yuko Kusakabe, Yoshiko Noguchi, Kaori Yuki, Shuhei Koide, Shiro Tara, Atsunori Saraya, Kazumasa Aoyama, Naoya Mimura, Satoru Miyagi, Masanori Inoue, Toru Wakamatsu, Tomoko Saito, Sadahisa Ogasawara, Eiichiro Suzuki, Yoshihiko Ooka, Akinobu Tawada, Masayuki Otsuka, Masaru Miyazaki, Osamu Yokosuka, Atsushi Iwama
Histone H3 lysine 9 dimethylation (H3K9me2) is mainly regulated by the histone lysine methyltransferase G9a and is associated with the repression of transcription. However, both the role of G9a and the significance of H3K9me2 in hepatocellular carcinoma (HCC) cells remain unclear. In this study, we conducted loss-of-function assay of G9a using short-hairpin RNA and pharmacological interference. Knockdown of G9a reduced H3K9me2 levels and impaired both HCC cell growth and sphere formation. However, transforming growth factor β1-induced epithelial mesenchymal transition (EMT) was not suppressed by G9a knockdown...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28409176/systemic-analysis-of-osteoblast-specific-dna-methylation-marks-reveals-novel-epigenetic-basis-of-osteoblast-differentiation
#3
Fangtang Yu, Hui Shen, Hong-Wen Deng
DNA methylation is an important epigenetic modification that contributes to the lineage commitment and specific functions of different cell types. In this study, we compared ENCODE-generated genome-wide DNA methylation profiles of human osteoblast with 21 other types of human cells in order to identify osteoblast-specific methylation events. For most of the cell strains, data from two isogenic replicates were included, resulting in a total of 51 DNA methylation datasets. We identified 852 significant osteoblast-specific differentially methylated CpGs (DMCs) and 295 significant differentially methylated regions (DMRs)...
June 2017: Bone Reports
https://www.readbyqxmd.com/read/28407733/the-kr%C3%A3-ppel-like-factor-9-cistrome-in-mouse-hippocampal-neurons-reveals-predominant-transcriptional-repression-via-proximal-promoter-binding
#4
Joseph R Knoedler, Arasakumar Subramani, Robert J Denver
BACKGROUND: Krüppel-like factor 9 (Klf9) is a zinc finger transcription factor that functions in neural cell differentiation, but little is known about its genomic targets or mechanism of action in neurons. RESULTS: We used the mouse hippocampus-derived neuronal cell line HT22 to identify genes regulated by Klf9, and we validated our findings in mouse hippocampus. We engineered HT22 cells to express a Klf9 transgene under control of the tetracycline repressor, and used RNA sequencing to identify genes modulated by Klf9...
April 13, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28405676/ulinastatin-protects-against-lipopolysaccharide-induced-cardiac-microvascular-endothelial-cell-dysfunction-via-downregulation-of-lncrna-malat1-and-ezh2-in-sepsis
#5
Zhaoxia Yu, Aisa Rayile, Xiangyang Zhang, Ying Li, Qiang Zhao
The present study aimed to evaluate the effects of ulinastatin on the permeability and apoptosis of lipopolysaccharide (LPS)-induced cardiac microvascular endothelial cells (CMVECs), and investigate its molecular mechanisms in sepsis. The sepsis rat model was induced by cecal ligation and puncture (CLP), and rat CMVECs were isolated and treated with LPS or/and ulinastatin. Then, cell permeability was evaluated by transendothelial electrical resistance, reactive oxygen species (ROS) levels were assessed by 2,7-dichlorofluorescein diacetate, cell apoptosis was detected using Annexin V-FITC apoptosis detection kit, and the expression levels of Bcl-2, Bax, caspase-3, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and EZH2 were detected by RT-qPCR and/or western blotting...
May 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28404620/accumulation-of-rna-on-chromatin-disrupts-heterochromatic-silencing
#6
Cornelia Brönner, Luca Salvi, Manuel Zocco, Ilaria Ugolini, Mario Halic
Long non-coding RNAs (lncRNAs) play a conserved role in regulating gene expression, chromatin dynamics and cell differentiation. They serve as a platform for RNA interference (RNAi)-mediated heterochromatin formation or DNA methylation in many eukaryotic organisms. We found in Schizosaccharomyces pombe, that heterochromatin is lost at transcribed regions in absence of RNA degradation. We show that heterochromatic RNAs are retained on chromatin, form DNA:RNA hybrids and need to be degraded by the Ccr4-Not complex or RNAi to maintain heterochromatic silencing...
April 12, 2017: Genome Research
https://www.readbyqxmd.com/read/28402947/overexpression-of-the-transcription-factor-atf3-with-a-regulatory-molecular-signature-associates-with-the-pathogenic-development-of-colorectal-cancer
#7
Feng Yan, Le Ying, Xiaofang Li, Bin Qiao, Qiaohong Meng, Liang Yu, Xiangliang Yuan, Shu-Ting Ren, David W Chan, Liyun Shi, Peihua Ni, Xuefeng Wang, Dakang Xu, Yiqun Hu
The identification of novel biomarkers of cancer is important for improved diagnosis and prognosis. With an abundant amount of resources in the publicly available database, such as the Cancer Genome Atlas (TCGA) database, an integrative strategy is used to systematically characterize the aberrant patterns of colorectal cancer (CRC) based on RNA-Seq, chromatin immunoprecipitation sequencing (ChIP-Seq), tissue microarray (TMA), gene profiling and molecular signatures. The expression of the transcription factor ATF3 was elevated in human CRC specimens in a TMA by immunochemistry analysis compared to the adjacent normal tissues...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28399266/pirna-3312-a-putative-role-for-pyrethroid-resistance-in-culex-pipiens-pallens-diptera-culicidae
#8
Juxin Guo, Wenyun Ye, Xianmiao Liu, Xueli Sun, Qin Guo, Yun Huang, Lei Ma, Yan Sun, Bo Shen, Dan Zhou, Changliang Zhu
Piwi-interacting RNAs (piRNAs) are a newly identified class of small noncoding RNAs. They are associated with chromatin organization, messenger RNA stability, and genome structure. Although the overexpression of piRNA-3312 in deltamethrin-susceptible (DS) strain of Culex pipiens pallens (L.) was observed in our previous large-scale transcriptome data, the roles of piRNA in insecticide resistance have not been clearly defined. The aim of the present study was to investigate how piRNA-3312 is involved in insecticide resistance...
March 7, 2017: Journal of Medical Entomology
https://www.readbyqxmd.com/read/28398700/differential-requirements-for-dna-repair-proteins-in-immortalized-cell-lines-using-alternative-lengthening-of-telomere-mechanisms
#9
Alaina R Martinez, Zeenia Kaul, Jeffrey D Parvin, Joanna Groden
Cancer cells require telomere maintenance to enable uncontrolled growth. Most often telomerase is activated, although a subset of human cancers are telomerase-negative and depend on recombination-based mechanisms known as ALT (Alternative Lengthening of Telomeres). ALT depends on proteins that are essential for homologous recombination, including BLM and the MRN complex, to extend telomeres. This study surveyed the requirement for requisite homologous recombination proteins, yet to be studied in human ALT cell lines, by protein depletion using RNA interference...
April 11, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28398509/mll3-mll4-are-required-for-cbp-p300-binding-on-enhancers-and-super-enhancer-formation-in-brown-adipogenesis
#10
Binbin Lai, Ji-Eun Lee, Younghoon Jang, Lifeng Wang, Weiqun Peng, Kai Ge
Histone H3K4me1/2 methyltransferases MLL3/MLL4 and H3K27 acetyltransferases CBP/p300 are major enhancer epigenomic writers. To understand how these epigenomic writers orchestrate enhancer landscapes in cell differentiation, we have profiled genomic binding of MLL4, CBP, lineage-determining transcription factors (EBF2, C/EBPβ, C/EBPα, PPARγ), coactivator MED1, RNA polymerase II, as well as epigenome (H3K4me1/2/3, H3K9me2, H3K27me3, H3K36me3, H3K27ac), transcriptome and chromatin opening during adipogenesis of immortalized preadipocytes derived from mouse brown adipose tissue (BAT)...
April 8, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28393894/loss-of-polycomb-group-protein-pcgf1-severely-compromises-proper-differentiation-of-embryonic-stem-cells
#11
Yun Yan, Wukui Zhao, Yikai Huang, Huan Tong, Yin Xia, Qing Jiang, Jinzhong Qin
The Polycomb repressive complex 1 (PRC1) is essential for fate decisions of embryonic stem (ES) cells. Emerging evidence suggests that six major variants of PRC1 complex, defined by the mutually exclusive presence of Pcgf subunit, regulate distinct biological processes, yet very little is known about the mechanism by which each version of PRC1 instructs and maintains cell fate. Here, we disrupted the Pcgf1, also known as Nspc1 and one of six Pcgf paralogs, in mouse ES cells by the CRISPR/Cas9 technology. We showed that although these mutant cells were viable and retained normal self-renewal, they displayed severe defects in differentiation in vitro...
April 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28388877/evolutionary-acquisition-of-promoter-associated-non-coding-rna-pancrna-repertoires-diversifies-species-dependent-gene-activation-mechanisms-in-mammals
#12
Masahiro Uesaka, Kiyokazu Agata, Takao Oishi, Kinichi Nakashima, Takuya Imamura
BACKGROUND: Recent transcriptome analyses have shown that long non-coding RNAs (ncRNAs) play extensive roles in transcriptional regulation. In particular, we have reported that promoter-associated ncRNAs (pancRNAs) activate the partner gene expression via local epigenetic changes. RESULTS: Here, we identify thousands of genes under pancRNA-mediated transcriptional activation in five mammalian species in common. In the mouse, 1) pancRNA-partnered genes confined their expression pattern to certain tissues compared to pancRNA-lacking genes, 2) expression of pancRNAs was significantly correlated with the enrichment of active chromatin marks, H3K4 trimethylation and H3K27 acetylation, at the promoter regions of the partner genes, 3) H3K4me1 marked the pancRNA-partnered genes regardless of their expression level, and 4) C- or G-skewed motifs were exclusively overrepresented between-200 and-1 bp relative to the transcription start sites of the pancRNA-partnered genes...
April 7, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28377872/dna-methylation-alters-transcriptional-rates-of-differentially-expressed-genes-and-contributes-to-pathophysiology-in-mice-fed-a-high-fat-diet
#13
Pili Zhang, Tianjiao Chu, N Dedousis, Benjamin S Mantell, Ian Sipula, Lucy Li, Kimberly D Bunce, Patricia A Shaw, Liora S Katz, Jun Zhu, Carmen Argmann, Robert M O'Doherty, David G Peters, Donald K Scott
OBJECTIVE: Overnutrition can alter gene expression patterns through epigenetic mechanisms that may persist through generations. However, it is less clear if overnutrition, for example a high fat diet, modifies epigenetic control of gene expression in adults, or by what molecular mechanisms, or if such mechanisms contribute to the pathology of the metabolic syndrome. Here we test the hypothesis that a high fat diet alters hepatic DNA methylation, transcription and gene expression patterns, and explore the contribution of such changes to the pathophysiology of obesity...
April 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28375666/glucocorticoid-receptor-chip-seq-identifies-plcd1-as-a-klf15-target-that-represses-airway-smooth-muscle-hypertrophy
#14
Sarah K Sasse, Vineela Kadiyala, Thomas Danhorn, Reynold A Panettieri, Tzu L Phang, Anthony N Gerber
Glucocorticoids exert important therapeutic effects on airway smooth muscle (ASM), yet few direct targets of glucocorticoid signaling in ASM have been definitively identified. Here, we show that the transcription factor, KLF15, is directly induced by glucocorticoids in primary human ASM and that KLF15 represses ASM hypertrophy. We integrated transcriptome data from KLF15 overexpression with genome-wide analysis of RNA Polymerase II (RNAPII) and glucocorticoid receptor (GR) occupancy (i.e. ChIP-seq) to identify PLCD1 as both a KLF15-regulated gene and a novel repressor of ASM hypertrophy...
April 4, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28368536/transcription-factor-crem-mediates-high-glucose-response-in-cardiomyocytes-and-in-a-male-mouse-model-of-prolonged-hyperglycemia
#15
Saviana A Barbati, Claudia Colussi, Lorenza Bacci, Aurora Aiello, Agnese Re, Egidio Stigliano, Andrea M Isidori, Claudio Grassi, Alfredo Pontecorvi, Antonella Farsetti, Carlo Gaetano, Simona Nanni
This study aims at investigating the epigenetic landscape of cardiomyocytes exposed to long elevated glucose levels in vitro and in vivo Exposure of mouse HL-1 and rat differentiated H9C2 cardiomyocyte cell lines to high glucose (30 mM) for 72 hours determined some epigenetic changes including upregulation of class I and III HDAC protein levels and activity, inhibition of histone acetylase p300 activity, increase in histone H3 lysine (K) 27 trimethylation (H3K27me3) and reduction in H3K9 acetylation (H3K9Ac)...
March 22, 2017: Endocrinology
https://www.readbyqxmd.com/read/28367307/transcriptome-analysis-of-microglia-in-a-mouse-model-of-rett-syndrome-differential-expression-of-genes-associated-with-microglia-macrophage-activation-and-cellular-stress
#16
Dejian Zhao, Ryan Mokhtari, Erika Pedrosa, Rayna Birnbaum, Deyou Zheng, Herbert M Lachman
BACKGROUND: Rett syndrome (RTT) is a severe, neurodevelopmental disorder primarily affecting girls, characterized by progressive loss of cognitive, social, and motor skills after a relatively brief period of typical development. It is usually due to de novo loss of function mutations in the X-linked gene, MeCP2, which codes for the gene expression and chromatin regulator, methyl-CpG binding protein 2. Although the behavioral phenotype appears to be primarily due to neuronal Mecp2 deficiency in mice, other cell types, including astrocytes and oligodendrocytes, also appear to contribute to some aspects of the RTT phenotype...
2017: Molecular Autism
https://www.readbyqxmd.com/read/28361350/foxm1-transcriptionally-regulates-expression-of-integrin-%C3%AE-1-in-triple-negative-breast-cancer
#17
Zuhal Hamurcu, Nermin Kahraman, Ahmed Ashour, Bulent Ozpolat
PURPOSE: Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer and associated with early metastasis, drug resistance, and poor patient survival. Fork head box M1 (FOXM1) is considered as an emerging molecular target due to its oncogenic role and high overexpression profile in 85% in TNBC. However, molecular mechanisms by which FOXM1 transcription factor mediate its oncogenic effects are not fully understood. Integrin β1 is often upregulated in invasive breast cancers and associated with poor clinical outcome and shorter overall patient survival in TNBC...
March 30, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28358873/whole-genome-analysis-of-papillary-kidney-cancer-finds-significant-noncoding-alterations
#18
Shantao Li, Brian M Shuch, Mark B Gerstein
To date, studies on papillary renal-cell carcinoma (pRCC) have largely focused on coding alterations in traditional drivers, particularly the tyrosine-kinase, Met. However, for a significant fraction of tumors, researchers have been unable to determine a clear molecular etiology. To address this, we perform the first whole-genome analysis of pRCC. Elaborating on previous results on MET, we find a germline SNP (rs11762213) in this gene predicting prognosis. Surprisingly, we detect no enrichment for small structural variants disrupting MET...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28352075/elevated-cox-2-expression-promotes-angiogenesis-through-egfr-p38-mapk-sp1-dependent-signalling-in-pancreatic-cancer
#19
Hai Hu, Ting Han, Meng Zhuo, Lei-Lei Wu, Cuncun Yuan, Lixia Wu, Wang Lei, Feng Jiao, Li-Wei Wang
Cyclooxygenase-2 (COX-2) was stated to be overexpression in various human malignancies associating with angiogenesis, metastasis and chemoresistence. Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease displaying many of these characteristics. A common abnormality of PDAC is overexpression of specificity protein-1 (Sp1), which was said to correlate with malignant phenotypes of human cancers. Using RNA-seq data from The Cancer Genome Atlas (TCGA), we found that Sp1 expression was positively correlated with that of COX-2 in PDAC, and that the inhibition or overexpression of Sp1 in PDAC cells leads to decreased or elevated COX-2 expression...
March 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28351991/the-composition-of-the-arabidopsis-rna-polymerase-ii-transcript-elongation-complex-reveals-the-interplay-between-elongation-and-mrna-processing-factors
#20
Wojciech Antosz, Alexander Pfab, Hans F Ehrnsberger, Philipp Holzinger, Karin Köllen, Simon A Mortensen, Astrid Bruckmann, Thomas Schubert, Gernot Längst, Joachim Griesenbeck, Veit Schubert, Marion Grasser, Klaus D Grasser
Transcript elongation factors (TEFs) are a heterogeneous group of proteins that control the efficiency of transcript elongation of subsets of genes by RNA polymerase II (RNAPII) in the chromatin context. Using reciprocal tagging in combination with affinity-purification and mass spectrometry, we demonstrate that in Arabidopsis thaliana, the TEFs SPT4/SPT5, SPT6, FACT, PAF1-C, and TFIIS co-purified with each other and with elongating RNAPII, while P-TEFb was not among the interactors. Additionally, NAP1 histone chaperones, ATP-dependent chromatin remodelling factors, and some histone-modifying enzymes including Elongator were repeatedly found associated with TEFs...
March 28, 2017: Plant Cell
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