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Transcriptional elongation

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https://www.readbyqxmd.com/read/28350987/the-super-elongation-complex-drives-neural-stem-cell-fate-commitment
#1
Kun Liu, Dan Shen, Jingwen Shen, Shihong M Gao, Bo Li, Chouin Wong, Weidong Feng, Yan Song
Asymmetric stem cell division establishes an initial difference between a stem cell and its differentiating sibling, critical for maintaining homeostasis and preventing carcinogenesis. Yet the mechanisms that consolidate and lock in such initial fate bias remain obscure. Here, we use Drosophila neuroblasts to demonstrate that the super elongation complex (SEC) acts as an intrinsic amplifier to drive cell fate commitment. SEC is highly expressed in neuroblasts, where it promotes self-renewal by physically associating with Notch transcription activation complex and enhancing HES (hairy and E(spl)) transcription...
March 27, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28345603/pja2-ubiquitinates-the-hiv-1-tat-protein-with-atypical-chain-linkages-to-activate-viral-transcription
#2
Tyler B Faust, Yang Li, Gwendolyn M Jang, Jeffrey R Johnson, Shumin Yang, Amit Weiss, Nevan J Krogan, Alan D Frankel
Transcription complexes that assemble at the HIV-1 promoter efficiently initiate transcription but generate paused RNA polymerase II downstream from the start site. The virally encoded Tat protein hijacks positive transcription elongation factor b (P-TEFb) to phosphorylate and activate this paused polymerase. In addition, Tat undergoes a series of reversible post-translational modifications that regulate distinct steps of the transcription cycle. To identify additional functionally important Tat cofactors, we performed RNAi knockdowns of sixteen previously identified Tat interactors and found that a novel E3 ligase, PJA2, ubiquitinates Tat in a non-degradative manner and specifically regulates the step of HIV transcription elongation...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28340332/super-elongation-complex-promotes-early-hiv-transcription-and-its-function-is-modulated-by-p-tefb
#3
Alona Kuzmina, Simona Krasnopolsky, Ran Taube
Early work on the control of transcription of the human immunodeficiency virus (HIV) laid the foundation for our current knowledge of how RNA Polymerase II is released from promoter-proximal pausing sites and transcription elongation is enhanced. The viral Tat activator recruits Positive Transcription Elongation Factor b (P-TEFb) and Super Elongation Complex (SEC) that jointly drive transcription elongation. While substantial progress in understanding the role of SEC in HIV gene transcription elongation has been obtained, defining of the mechanisms that govern SEC functions is still limited, and the role of SEC in controlling HIV transcription in the absence of Tat is less clear...
February 17, 2017: Transcription
https://www.readbyqxmd.com/read/28337836/plant-transcription-factors-from-the-homeodomain-leucine-zipper-family-i-role-in-development-and-stress-responses
#4
REVIEW
María Florencia Perotti, Pamela Anahí Ribone, Raquel Lía Chan
In front of stressful conditions plants display adaptation mechanisms leading to changes in their morphology, physiology, development and molecular composition. Transcription factors (TFs) play crucial roles in these complex adaptation processes. This work is focused in the homeodomain-leucine zipper I (HD-Zip I) family of TFs, unique to plants. First discovered in 1991, they were identified and isolated from monocotyledonous and dicotyledonous plants showing high structural similarity and diversified functions...
March 24, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28336775/nelf-e-is-recruited-to-dna-double-strand-break-sites-to-promote-transcriptional-repression-and-repair
#5
Samah W Awwad, Enas R Abu-Zhayia, Noga Guttmann-Raviv, Nabieh Ayoub
Double-strand breaks (DSBs) trigger rapid and transient transcription pause to prevent collisions between repair and transcription machineries at damage sites. Little is known about the mechanisms that ensure transcriptional block after DNA damage. Here, we reveal a novel role of the negative elongation factor NELF in blocking transcription activity nearby DSBs. We show that NELF-E and NELF-A are rapidly recruited to DSB sites. Furthermore, NELF-E recruitment and its repressive activity are both required for switching off transcription at DSBs...
March 23, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28334900/cdk12-regulates-alternative-last-exon-mrna-splicing-and-promotes-breast-cancer-cell-invasion
#6
Jerry F Tien, Alborz Mazloomian, S-W Grace Cheng, Christopher S Hughes, Christalle C T Chow, Leanna T Canapi, Arusha Oloumi, Genny Trigo-Gonzalez, Ali Bashashati, James Xu, Vicky C-D Chang, Sohrab P Shah, Samuel Aparicio, Gregg B Morin
CDK12 (cyclin-dependent kinase 12) is a regulatory kinase with evolutionarily conserved roles in modulating transcription elongation. Recent tumor genome studies of breast and ovarian cancers highlighted recurrent CDK12 mutations, which have been shown to disrupt DNA repair in cell-based assays. In breast cancers, CDK12 is also frequently co-amplified with the HER2 (ERBB2) oncogene. The mechanisms underlying functions of CDK12 in general and in cancer remain poorly defined. Based on global analysis of mRNA transcripts in normal and breast cancer cell lines with and without CDK12 amplification, we demonstrate that CDK12 primarily regulates alternative last exon (ALE) splicing, a specialized subtype of alternative mRNA splicing, that is both gene- and cell type-specific...
March 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334711/quantitative-proteomics-analysis-of-ischemia-reperfusion-injury-modulated-proteins-in-cardiac-microvascular-endothelial-cells-and-the-protective-role-of-tongxinluo
#7
Qing Li, He-He Cui, Yue-Jin Yang, Xiang-Dong Li, Gui-Hao Chen, Xia-Qiu Tian, Chen Jin, Qiu-Ting Dong, Pei-Sen Huang, Jun Xu
BACKGROUND: The protection of endothelial cells (ECs) against reperfusion injury has received little attention. In this study, we used Tandem Mass Tag (TMT) labeling proteomics to investigate the modulated proteins in an in vitro model of cardiac microvascular endothelial cells (CMECs) subjected to ischemia/reperfusion (I/R) injury and their alteration by traditional Chinese medicine Tongxinluo (TXL). METHODS: Human CMECs were subjected to 2 h of hypoxia followed by 2 h of reoxygenation with different concentrations of TXL Protein expression profiles of CMECs were determined using tandem mass spectrometry...
March 24, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28334513/the-number-of-cag-and-ggn-triplet-repeats-in-the-androgen-receptor-gene-exert-combinatorial-effect-on-hormonal-and-sperm-parameters-in-young-men
#8
M Grigorova, M Punab, T Kahre, M Ivandi, N Tõnisson, O Poolamets, V Vihljajev, B Žilaitienė, J Erenpreiss, V Matulevičius, M Laan
Androgen receptor (AR) is a transcription factor that is activated upon binding to testosterone (T) and is implicated in regulating the expression of reproduction-related genes. The human AR gene (Xq11-12) spans 186,588 bp and eight exons. N-terminal transactivation domain of the encoded AR protein harbours two polymorphic stretches of identical amino acids, a polyglutamine tract (encoded by 8-37 CAG-repeats) and a polyglycine tract (encoded by 10-30 GGN-repeats). We set forward to analyse independent and combinatory effects of the length of these repetitive tracts on male reproductive hormones, testicular and sperm parameters in a population-based cohort of Baltic young men (n = 974; aged 20...
March 23, 2017: Andrology
https://www.readbyqxmd.com/read/28332923/different-types-of-pausing-modes-during-transcription-initiation
#9
Eitan Lerner, Antonino Ingargiola, Jookyung J Lee, Sergei Borukhov, Xavier Michalet, Shimon Weiss
In many cases, initiation is rate limiting to transcription. This due in part to the multiple cycles of abortive transcription that delay promoter escape and the transition from initiation to elongation. Pausing of transcription in initiation can further delay promoter escape. The previously hypothesized pausing in initiation was confirmed by two recent studies from Duchi et al. (1) and from Lerner, Chung et al. (2) In both studies, pausing is attributed to lack of forward translocation of the nascent transcript during initiation...
March 23, 2017: Transcription
https://www.readbyqxmd.com/read/28332716/mir-124-and-mir-9-mediated-downregulation-of-hdac5-promotes-neurite-development-through-activating-mef2c-gpm6a-pathway
#10
Xi Gu, Congcong Fu, Lifang Lin, Shuhu Liu, Xiaohong Su, Aili Li, Qiaoqi Wu, Chunhong Jia, Peidong Zhang, Lu Chen, Xinhong Zhu, Xuemin Wang
The class IIa histone deacetylases (HDACs) play important roles in the central nervous system during diverse biological processes such as synaptic plasticity, axon regeneration, cell apoptosis, and neural differentiation. Although it is known that HDAC5 regulates neuronal differentiation, neither the physiological function nor the regulation of HDAC5 in neuronal differentiation is clear. Here, we identify HDAC5 as an inhibitor of neurite elongation and show that HDAC5 is regulated by the brain enriched microRNA miR-124 and miR-9...
March 23, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28330952/effects-of-insulin-and-the-glucagon-like-peptide-1-receptor-agonist-liraglutide-on-the-kidney-proteome-in-db-db-mice
#11
Leena Liljedahl, Jenny Norlin, James N McGuire, Peter James
Diabetes mellitus (DM) is a worldwide disease that affects 9% of the adult world population and type 2 DM accounts for 90% of those. A common consequence of DM is kidney complications, which could lead to kidney failure. We studied the potential effects of treatment with insulin and the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide on the diabetic kidney proteome through the use of the db/db mouse model system and mass spectrometry (MS). Multivariate analyses revealed distinct effects of insulin and liraglutide on the db/db kidney proteome, which was seen on the protein levels of, for example, pterin-4 α-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor-1α (PCBD1), neural precursor cell expressed developmentally down-regulated-8 (NEDD8), transcription elongation factor-B polypeptide-1 (ELOC) and hepcidin (HEPC)...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28330559/dge-seq-analysis-of-mur3-related-arabidopsis-mutants-provides-insight-into-how-dysfunctional-xyloglucan-affects-cell-elongation
#12
Zongchang Xu, Meng Wang, Dachuan Shi, Gongke Zhou, Tiantian Niu, Michael G Hahn, Malcolm A O'Neill, Yingzhen Kong
Our previous study of the Arabidopsis mur3-3 mutant and mutant plants in which the mur3-3 phenotypes are suppressed (xxt2mur3-3, xxt5mur3-3, xxt1xxt2mur3-3 and 35Spro:XLT2:mur3-3) showed that hypocotyl cell elongation is decreased in plants that synthesize galactose-deficient xyloglucan. To obtain genome-wide insight into the transcriptome changes and regulatory networks that may be involved in this decreased elongation, we performed digital gene expression analyses of the etiolated hypocotyls of wild type (WT), mur3-3 and the four suppressor lines...
May 2017: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/28329910/nucleosome-mobility-and-the-regulation-of-gene-expression-insights-from-single-molecule-studies
#13
REVIEW
Sergei Rudnizky, Omri Malik, Adaiah Bavly, Lilach Pnueli, Philippa Melamed, Ariel Kaplan
Nucleosomes at the promoters of genes regulate the accessibility of the transcription machinery to DNA, and function as a basic layer in the complex regulation of gene expression. Our understanding of the role of the nucleosome's spontaneous, thermally driven position changes in modulating expression is lacking. This is the result of the paucity of experimental data on these dynamics, at high-resolution, and for DNA sequences that belong to real, transcribed genes. We have developed an assay that uses partial, reversible unzipping of nucleosomes with optical tweezers to repeatedly probe a nucleosome's position over time...
March 22, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28326087/arabidopsis-nac-transcription-factor-jungbrunnen1-exerts-conserved-control-over-gibberellin-and-brassinosteroid-metabolism-and-signaling-genes-in-tomato
#14
Sara Shahnejat-Bushehri, Annapurna D Allu, Nikolay Mehterov, Venkatesh P Thirumalaikumar, Saleh Alseekh, Alisdair R Fernie, Bernd Mueller-Roeber, Salma Balazadeh
The Arabidopsis thaliana NAC transcription factor JUNGBRUNNEN1 (AtJUB1) regulates growth by directly repressing GA3ox1 and DWF4, two key genes involved in gibberellin (GA) and brassinosteroid (BR) biosynthesis, respectively, leading to GA and BR deficiency phenotypes. AtJUB1 also reduces the expression of PIF4, a bHLH transcription factor that positively controls cell elongation, while it stimulates the expression of DELLA genes, which are important repressors of growth. Here, we extend our previous findings by demonstrating that AtJUB1 induces similar GA and BR deficiency phenotypes and changes in gene expression when overexpressed in tomato (Solanum lycopersicum)...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28323168/production-and-characterization-of-a-highly-pure-rna-polymerase-holoenzyme-from-mycobacterium-tuberculosis
#15
Omar Herrera-Asmat, Lucyna Lubkowska, Mikhail Kashlev, Carlos J Bustamante, Daniel G Guerra, Maria L Kireeva
Recent publications have shown that active RNA polymerase (RNAP) from Mycobacterium tuberculosis (MtbRNAP) can be produced by expressing all four subunits in a single recombinant Escherichia coli strain [1-3]. By reducing the number of plasmids and changing the codon usage of the Mtb genes in the co-expression system published by Banerjee et al. [1], we present a simplified, detailed and reproducible protocol for the purification of recombinant MtbRNAP containing the ω subunit. Moreover, we describe the formation of ternary elongation complexes (TECs) with a short fluorescence-labeled RNA primer and DNA oligonucleotides, suitable for transcription elongation studies...
March 18, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28322550/multiplex-substrate-profiling-by-mass-spectrometry-for-kinases-reveals-quantitative-substrate-motifs
#16
Nicole Olson Meyer, Anthony J O'Donoghue, Ursula Schulze-Gahmen, Matthew Ravalin, Steven M Moss, Michael B Winter, Giselle M Knudsen, Charles S Craik
The more than 500 protein kinases comprising the human kinome catalyze hundreds of thousands of phosphorylation events to regulate a diversity of cellular functions; however, the extended substrate specificity is still unknown for many of these kinases. We report here a method for quantitatively describing kinase substrate specificity using an unbiased peptide library-based approach with direct measurement of phosphorylation by tandem LC-MS/MS peptide sequencing (Multiplex Substrate Profiling by Mass Spectrometry, MSP-MS)...
March 21, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28321936/jasmonate-inhibits-cop1-activity-to-suppress-hypocotyl-elongation-and-promote-cotyledon-opening-in-etiolated-arabidopsis-seedlings
#17
Yuyu Zheng, Xuefei Cui, Liang Su, Shuang Fang, Jinfang Chu, Qingqiu Gong, Jianping Yang, Ziqiang Zhu
A germinating seedling undergoes skotomorphogenesis to emerge from the soil and reach for light. During this phase, the cotyledons are closed, and the hypocotyl elongates. Upon exposure to light, the seedling rapidly switches to photomorphogenesis by opening its cotyledons and suppressing hypocotyl elongation. The E3 ubiquitin ligase CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) is critical for maintaining skotomorphogenesis. Here, we report that jasmonate (JA) suppresses hypocotyl elongation and stimulates cotyledon opening in etiolated seedlings, partially phenocopying cop1 mutants in the dark...
March 20, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28320505/fine-tuning-of-gene-expression-dynamics-by-the-set2-rpd3s-pathway
#18
Bo Bae Lee, Ji Hyun Kim, TaeSoo Kim
RNA polymerase II-interacting the Set2 methyltransferase co-transcriptionally methylates histone H3 at lysine 36 within the body of genes. This modification facilitates histone deacetylation by Rpd3S HDAC in 3' transcribed regions to suppress cryptic initiation and slow elongation. Although this pathway is important for global deacetylation, no strong effects on genome-wide transcription have been seen under optimized laboratory conditions. In contrast, this pathway slows the kinetics of mRNA induction when target genes are induced upon environmental changes...
March 21, 2017: BMB Reports
https://www.readbyqxmd.com/read/28318822/genome-wide-analysis-of-rna-polymerase-ii-termination-at-protein-coding-genes
#19
Carlo Baejen, Jessica Andreani, Phillipp Torkler, Sofia Battaglia, Bjoern Schwalb, Michael Lidschreiber, Kerstin C Maier, Andrea Boltendahl, Petra Rus, Stephanie Esslinger, Johannes Söding, Patrick Cramer
At the end of protein-coding genes, RNA polymerase (Pol) II undergoes a concerted transition that involves 3'-processing of the pre-mRNA and transcription termination. Here, we present a genome-wide analysis of the 3'-transition in budding yeast. We find that the 3'-transition globally requires the Pol II elongation factor Spt5 and factors involved in the recognition of the polyadenylation (pA) site and in endonucleolytic RNA cleavage. Pol II release from DNA occurs in a narrow termination window downstream of the pA site and requires the "torpedo" exonuclease Rat1 (XRN2 in human)...
March 6, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28318486/structural-basis-of-transcription-arrest-by-coliphage-hk022-nun-in-an-escherichia-coli-rna-polymerase-elongation-complex
#20
Jin Young Kang, Paul Dominic B Olinares, James Chen, Elizabeth A Campbell, Arkady Mustaev, Brian T Chait, Max E Gottesman, Seth A Darst
Coliphage HK022 Nun blocks superinfection by coliphage λ by stalling RNA polymerase (RNAP) translocation specifically on λΔNA.To provide a structural framework to understand how Nun blocks RNAP translocation, we determined structures of Escherichia coli RNAP ternary elongation complexes (TECs) with and without Nun by single-particle cryo-electron microscopy. Nun fits tightly into the TEC by taking advantage of gaps between the RNAP and the nucleic acids. The C-terminal segment of Nun interacts with the RNAP β and β' subunits inside the RNAP active site cleft as well as with nearly every element of the nucleic-acid scaffold, essentially crosslinking the RNAP and the nucleic acids to prevent translocation, a mechanism supported by the effects of Nun amino acid substitutions...
March 20, 2017: ELife
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