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Promoter proximal pausing

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https://www.readbyqxmd.com/read/28451632/skill-learning-modulates-rna-pol-ii-poising-at-immediate-early-genes-in-the-adult-striatum
#1
Pedro Galvão-Ferreira, Michal Lipinski, Fernando Santos, Angel Barco, Rui M Costa
A multilayered complexity of epigenetic and transcriptional regulatory mechanisms underlies neuronal activity-dependent gene transcription. The regulation of RNA Pol II progression along the transcription cycle, from promoter-proximal poising (with RNA Pol II paused at promoter-proximal regions, characterized by a Ser5P(+)-rich and Ser2P(+)-poor RPB1 CTD) to active elongation, has emerged as a major step in transcriptional regulation across several organisms, tissues, and developmental stages, including the nervous system...
March 2017: ENeuro
https://www.readbyqxmd.com/read/28396559/an-mrna-capping-enzyme-targets-fact-to-the-active-gene-to-enhance-the-engagement-of-rna-polymerase-ii-into-transcriptional-elongation
#2
Rwik Sen, Amala Kaja, Jannatul Ferdoush, Shweta Lahudkar, Priyanka Barman, Sukesh R Bhaumik
We have recently demonstrated that an mRNA-capping enzyme, Cet1, impairs promoter proximal accumulation/pausing of RNA polymerase II (pol-II) independently of its capping activity in Saccharomyces cerevisiae to control transcription. However, it is yet unknown how pol-II pausing is regulated by Cet1. Here, we show that Cet1's N-terminal domain (NTD) promotes the recruitment of FACT (FAcilitates Chromatin Transcription that enhances engagement of pol-II into transcriptional elongation) to the coding sequence of an active gene, ADH1, independently of mRNA-capping activity...
April 10, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28363125/pause-go-from-the-discovery-of-rna-polymerase-pausing-to-its-functional-implications
#3
REVIEW
Andreas Mayer, Heather M Landry, L Stirling Churchman
The synthesis of nascent RNA is a discontinuous process in which phases of productive elongation by RNA polymerase are interrupted by frequent pauses. Transcriptional pausing was first observed decades ago, but was long considered to be a special feature of transcription at certain genes. This view was challenged when studies using genome-wide approaches revealed that RNA polymerase II pauses at promoter-proximal regions in large sets of genes in Drosophila and mammalian cells. High-resolution genomic methods uncovered that pausing is not restricted to promoters, but occurs globally throughout gene-body regions, implying the existence of key-rate limiting steps in nascent RNA synthesis downstream of transcription initiation...
March 28, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28360925/jmjd6-a-jmjc-dioxygenase-with-many-interaction-partners-and-pleiotropic-functions
#4
REVIEW
Janice Kwok, Marie O'Shea, David A Hume, Andreas Lengeling
Lysyl hydroxylation and arginyl demethylation are post-translational events that are important for many cellular processes. The jumonji domain containing protein 6 (JMJD6) has been reported to catalyze both lysyl hydroxylation and arginyl demethylation on diverse protein substrates. It also interacts directly with RNA. This review summarizes knowledge of JMJD6 functions that have emerged in the last 15 years and considers how a single Jumonji C (JmjC) domain-containing enzyme can target so many different substrates...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28340332/super-elongation-complex-promotes-early-hiv-transcription-and-its-function-is-modulated-by-p-tefb
#5
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/28273906/identifying-novel-transcriptional-and-epigenetic-features-of-nuclear-lamina-associated-genes
#6
Feinan Wu, Jie Yao
Because a large portion of the mammalian genome is associated with the nuclear lamina (NL), it is interesting to study how native genes resided there are transcribed and regulated. In this study, we report unique transcriptional and epigenetic features of nearly 3,500 NL-associated genes (NL genes). Promoter regions of active NL genes are often excluded from NL-association, suggesting that NL-promoter interactions may repress transcription. Active NL genes with higher RNA polymerase II (Pol II) recruitment levels tend to display Pol II promoter-proximal pausing, while Pol II recruitment and Pol II pausing are not correlated among non-NL genes...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28263964/total-rna-seq-to-identify-pharmacological-effects-on-specific-stages-of-mrna-synthesis
#7
Sarah A Boswell, Andrew Snavely, Heather M Landry, L Stirling Churchman, Jesse M Gray, Michael Springer
Pharmacological perturbation is a powerful tool for understanding mRNA synthesis, but identification of the specific steps of this multi-step process that are targeted by small molecules remains challenging. Here we applied strand-specific total RNA sequencing (RNA-seq) to identify and distinguish specific pharmacological effects on transcription and pre-mRNA processing in human cells. We found unexpectedly that the natural product isoginkgetin, previously described as a splicing inhibitor, inhibits transcription elongation...
May 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28245789/mechanisms-of-groucho-mediated-repression-revealed-by-genome-wide-analysis-of-groucho-binding-and-activity
#8
Michael Chambers, Wiam Turki-Judeh, Min Woo Kim, Kenny Chen, Sean D Gallaher, Albert J Courey
BACKGROUND: The transcriptional corepressor Groucho (Gro) is required for the function of many developmentally regulated DNA binding repressors, thus helping to define the gene expression profile of each cell during development. The ability of Gro to repress transcription at a distance together with its ability to oligomerize and bind to histones has led to the suggestion that Gro may spread along chromatin. However, much is unknown about the mechanism of Gro-mediated repression and about the dynamics of Gro targeting...
February 28, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28213523/identification-of-regions-in-the-spt5-subunit-of-drb-sensitivity-inducing-factor-dsif-that-are-involved-in-promoter-proximal-pausing
#9
Yijun Qiu, David S Gilmour
DRB sensitivity-inducing factor (DSIF or Spt4/5) is a conserved transcription elongation factor that both inhibits and stimulates transcription elongation in metazoans. In Drosophila and vertebrates, DSIF together with negative elongation factor (NELF) associates with RNA polymerase II during early elongation and causes RNA polymerase II to pause in the promoter-proximal region of genes. The mechanism of how DSIF establishes pausing is not known. We constructed Spt5 mutant forms of DSIF and tested their capacity to restore promoter-proximal pausing to DSIF-depleted Drosophila nuclear extracts...
March 31, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28102758/p-tefb-finding-its-ways-to-release-promoter-proximally-paused-rna-polymerase-ii
#10
You Li, Min Liu, Lin-Feng Chen, Ruichuan Chen
The release of a paused Pol II depends on the recruitment of P-TEFb. Recent studies showed that both active P-TEFb and inactive P-TEFb (7SK snRNP) can be recruited to the promoter regions of global genes by different mechanisms. Here, we summarize the recent advances on these distinct recruitment mechanisms.
January 19, 2017: Transcription
https://www.readbyqxmd.com/read/28077616/different-modes-of-enhancer-specific-regulation-by-runt-and-even-skipped-during-drosophila-segmentation
#11
Saiyu Hang, J Peter Gergen
The initial metameric expression of the Drosophila sloppy paired 1 (slp1) gene is controlled by two distinct cis-regulatory DNA elements that interact in a nonadditive manner to integrate inputs from transcription factors encoded by the pair-rule segmentation genes. We performed chromatin immunoprecipitation on reporter genes containing these elements in different embryonic genotypes to investigate the mechanism of their regulation. The distal early stripe element (DESE) mediates both activation and repression by Runt...
March 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27928053/%C3%AF-38-dependent-promoter-proximal-pausing-by-bacterial-rna-polymerase
#12
Ivan Petushkov, Daria Esyunina, Andrey Kulbachinskiy
Transcription initiation by bacterial RNA polymerase (RNAP) requires a variable σ subunit that directs it to promoters for site-specific priming of RNA synthesis. The principal σ subunit responsible for expression of house-keeping genes can bind the transcription elongation complex after initiation and induce RNAP pausing through specific interactions with promoter-like motifs in transcribed DNA. We show that the stationary phase and stress response σ38 subunit can also induce pausing by Escherichia coli RNAP on DNA templates containing promoter-like motifs in the transcribed regions...
April 7, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27889238/insights-into-nucleosome-organization-in-mouse-embryonic-stem-cells-through-chemical-mapping
#13
Lilien N Voong, Liqun Xi, Amy C Sebeson, Bin Xiong, Ji-Ping Wang, Xiaozhong Wang
Nucleosome organization influences gene activity by controlling DNA accessibility to transcription machinery. Here, we develop a chemical biology approach to determine mammalian nucleosome positions genome-wide. We uncovered surprising features of nucleosome organization in mouse embryonic stem cells. In contrast to the prevailing model, we observe that for nearly all mouse genes, a class of fragile nucleosomes occupies previously designated nucleosome-depleted regions around transcription start sites and transcription termination sites...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27729530/nascent-rna-sequencing-reveals-distinct-features-in-plant-transcription
#14
Jonathan Hetzel, Sascha H Duttke, Christopher Benner, Joanne Chory
Transcriptional regulation of gene expression is a major mechanism used by plants to confer phenotypic plasticity, and yet compared with other eukaryotes or bacteria, little is known about the design principles. We generated an extensive catalog of nascent and steady-state transcripts in Arabidopsis thaliana seedlings using global nuclear run-on sequencing (GRO-seq), 5'GRO-seq, and RNA-seq and reanalyzed published maize data to capture characteristics of plant transcription. De novo annotation of nascent transcripts accurately mapped start sites and unstable transcripts...
October 25, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27725713/systems-level-analysis-reveals-selective-regulation-of-aqp2-gene-expression-by-vasopressin
#15
Pablo C Sandoval, J'Neka S Claxton, Jae Wook Lee, Fahad Saeed, Jason D Hoffert, Mark A Knepper
Vasopressin-mediated regulation of renal water excretion is defective in a variety of water balance disorders in humans. It occurs in part through long-term mechanisms that regulate the abundance of the aquaporin-2 water channel in renal collecting duct cells. Here, we use deep DNA sequencing in mouse collecting duct cells to ask whether vasopressin signaling selectively increases Aqp2 gene transcription or whether it triggers a broadly targeted transcriptional network. ChIP-Seq quantification of binding sites for RNA polymerase II was combined with RNA-Seq quantification of transcript abundances to identify genes whose transcription is regulated by vasopressin...
October 11, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27716820/gdown1-associates-efficiently-with-rna-polymerase-ii-after-promoter-clearance-and-displaces-tfiif-during-transcript-elongation
#16
Elizabeth DeLaney, Donal S Luse
Pausing during the earliest stage of transcript elongation by RNA polymerase II (Pol II) is a nearly universal control point in metazoan gene expression. The substoichiometric Pol II subunit Gdown1 facilitates promoter proximal pausing in vitro in extract-based transcription reactions, out-competes the initiation/elongation factor TFIIF for binding to free Pol II and co-localizes with paused Pol II in vivo. However, we have shown that Gdown1 cannot functionally associate with the Pol II preinitiation complex (PIC), which contains TFIIF...
2016: PloS One
https://www.readbyqxmd.com/read/27564129/tbp-loading-by-af4-through-sl1-is-the-major-rate-limiting-step-in-mll-fusion-dependent-transcription
#17
Hiroshi Okuda, Satoshi Takahashi, Akifumi Takaori-Kondo, Akihiko Yokoyama
Gene rearrangement of the mixed lineage leukemia (MLL) gene causes leukemia by inducing the constitutive expression of a gene subset normally expressed only in the immature haematopoietic progenitor cells. MLL gene rearrangements often generate fusion products of MLL and a component of the AF4 family/ENL family/P-TEFb (AEP) complex. MLL-AEP fusion proteins have the potential of constitutively recruiting the P-TEFb elongation complex. Thus, it is hypothesized that relieving the promoter proximal pausing of RNA polymerase II is the rate-limiting step of MLL fusion-dependent transcription...
October 17, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27520065/rna-polymerase-ii-pausing-modulates-hematopoietic-stem-cell-emergence-in-zebrafish
#18
Qiwen Yang, Xiuli Liu, Ting Zhou, Jennifer Cook, Kim Nguyen, Xiaoying Bai
The promoter-proximal pausing of RNA polymerase II (Pol II) plays a critical role in regulating metazoan gene transcription. Despite the prevalence of Pol II pausing across the metazoan genomes, little is known about the in vivo effect of Pol II pausing on vertebrate development. We use the emergence of hematopoietic stem cells (HSCs) in zebrafish embryos as a model to investigate the role of Pol II pausing in vertebrate organogenesis. Disrupting Pol II pausing machinery causes a severe reduction of HSC specification, a defect that can be effectively rescued by inhibiting Pol II elongation...
September 29, 2016: Blood
https://www.readbyqxmd.com/read/27498870/high-resolution-mapping-of-rna-polymerases-identifies-mechanisms-of-sensitivity-and-resistance-to-bet-inhibitors-in-t-8-21-aml
#19
Yue Zhao, Qi Liu, Pankaj Acharya, Kristy R Stengel, Quanhu Sheng, Xiaofan Zhou, Hojoong Kwak, Melissa A Fischer, James E Bradner, Stephen A Strickland, Sanjay R Mohan, Michael R Savona, Bryan J Venters, Ming-Ming Zhou, John T Lis, Scott W Hiebert
Bromodomain and extra-terminal domain (BET) family inhibitors offer an approach to treating hematological malignancies. We used precision nuclear run-on transcription sequencing (PRO-seq) to create high-resolution maps of active RNA polymerases across the genome in t(8;21) acute myeloid leukemia (AML), as these polymerases are exceptionally sensitive to BET inhibitors. PRO-seq identified over 1,400 genes showing impaired release of promoter-proximal paused RNA polymerases, including the stem cell factor receptor tyrosine kinase KIT that is mutated in t(8;21) AML...
August 16, 2016: Cell Reports
https://www.readbyqxmd.com/read/27492368/transcription-factors-gaf-and-hsf-act-at-distinct-regulatory-steps-to-modulate-stress-induced-gene-activation
#20
Fabiana M Duarte, Nicholas J Fuda, Dig B Mahat, Leighton J Core, Michael J Guertin, John T Lis
The coordinated regulation of gene expression at the transcriptional level is fundamental to development and homeostasis. Inducible systems are invaluable when studying transcription because the regulatory process can be triggered instantaneously, allowing the tracking of ordered mechanistic events. Here, we use precision run-on sequencing (PRO-seq) to examine the genome-wide heat shock (HS) response in Drosophila and the function of two key transcription factors on the immediate transcription activation or repression of all genes regulated by HS...
August 1, 2016: Genes & Development
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