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https://www.readbyqxmd.com/read/27899651/a-permissive-chromatin-state-regulated-by-zfp281-aff3-in-controlling-the-imprinted-meg3-polycistron
#1
Yan Wang, Yang Shen, Qian Dai, Qian Yang, Yue Zhang, Xin Wang, Wei Xie, Zhuojuan Luo, Chengqi Lin
Genomic imprinting is an epigenetic regulation that leads to gene expression in a parent-of-origin specific manner. AFF3, the central component of the Super Elongation Complex-like 3 (SEC-L3), is enriched at both the intergenic-differentially methylated region (IG-DMR) and the Meg3 enhancer within the imprinted Dlk1-Dio3 locus to regulate the allele-specific gene expression in this locus. The localization of AFF3 to IG-DMR requires ZFP57. However, how AFF3 functions at the Meg3 enhancer in maintaining allele-specific gene expression remains unclear...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27679741/ddx6-transfers-p-tefb-kinase-to-the-af4-af4n-aff1-super-elongation-complex
#2
Fabian Mück, Silvia Bracharz, Rolf Marschalek
AF4/AFF1 and AF5/AFF4 are both backbones for the assembly of "super elongation complexes" (SECs) that exert 2 distinct functions after the recruitment of P-TEFb from the 7SK snRNP: (1) initiation and elongation of RNA polymerase II gene transcription, and (2) modification of transcribed gene regions by distinct histone methylation patterns. In this study we aimed to investigate one of the initial steps, namely how P-TEFb is transferred from 7SK snRNPs to the SECs. In particular, we were interested in the role of DDX6 that we have recently identified as part of the AF4 complex...
2016: American Journal of Blood Research
https://www.readbyqxmd.com/read/27558685/pseudouridylation-of-7sk-snrna-promotes-7sk-snrnp-formation-to-suppress-hiv-1-transcription-and-escape-from-latency
#3
Yang Zhao, John Karijolich, Britt Glaunsinger, Qiang Zhou
The 7SK snRNA sequesters P-TEFb, a general transcription elongation factor and human co-factor for HIV-1 Tat protein, into the catalytically inactive 7SK snRNP Little is known about how 7SK RNA is regulated to perform this function. Here, we show that most of 7SK is pseudouridylated at position U250 by the predominant cellular pseudouridine synthase machinery, the DKC1-box H/ACA RNP Pseudouridylation is critical to stabilize 7SK snRNP, as its abolishment by either mutation at or around U250 or depletion of DKC1, the catalytic component of the box H/ACA RNP, disrupts 7SK snRNP and releases P-TEFb to form the super elongation complex (SEC) and the Brd4-P-TEFb complex...
October 2016: EMBO Reports
https://www.readbyqxmd.com/read/27353326/multiple-p-tefbs-cooperatively-regulate-the-release-of-promoter-proximally-paused-rna-polymerase-ii
#4
Xiaodong Lu, Xinxing Zhu, You Li, Min Liu, Bin Yu, Yu Wang, Muhua Rao, Haiyang Yang, Kai Zhou, Yao Wang, Yanheng Chen, Meihua Chen, Songkuan Zhuang, Lin-Feng Chen, Runzhong Liu, Ruichuan Chen
The association of DSIF and NELF with initiated RNA Polymerase II (Pol II) is the general mechanism for inducing promoter-proximal pausing of Pol II. However, it remains largely unclear how the paused Pol II is released in response to stimulation. Here, we show that the release of the paused Pol II is cooperatively regulated by multiple P-TEFbs which are recruited by bromodomain-containing protein Brd4 and super elongation complex (SEC) via different recruitment mechanisms. Upon stimulation, Brd4 recruits P-TEFb to Spt5/DSIF via a recruitment pathway consisting of Med1, Med23 and Tat-SF1, whereas SEC recruits P-TEFb to NELF-A and NELF-E via Paf1c and Med26, respectively...
August 19, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27310306/collaboration-of-mllt1-enl-polycomb-and-atm-for-transcription-and-genome-integrity
#5
Ayako Ui, Akira Yasui
Polycomb group (PcG) repress, whereas Trithorax group (TrxG) activate transcription for tissue development and cellular proliferation, and misregulation of these factors is often associated with cancer. ENL (MLLT1) and AF9 (MLLT3) are fusion partners of Mixed Lineage Leukemia (MLL), TrxG proteins, and are factors in Super Elongation Complex (SEC). SEC controls transcriptional elongation to release RNA polymerase II, paused around transcription start site. In MLL rearranged leukemia, several components of SEC have been found as MLL-fusion partners and the control of transcriptional elongation is misregulated leading to tumorigenesis in MLL-SEC fused Leukemia...
April 25, 2016: Nucleus
https://www.readbyqxmd.com/read/27292648/t-bet-activates-th1-genes-through-mediator-and-the-super-elongation-complex
#6
Arnulf Hertweck, Catherine M Evans, Malihe Eskandarpour, Jonathan C H Lau, Kristine Oleinika, Ian Jackson, Audrey Kelly, John Ambrose, Peter Adamson, David J Cousins, Paul Lavender, Virginia L Calder, Graham M Lord, Richard G Jenner
The transcription factor T-bet directs Th1 cell differentiation, but the molecular mechanisms that underlie this lineage-specific gene regulation are not completely understood. Here, we show that T-bet acts through enhancers to allow the recruitment of Mediator and P-TEFb in the form of the super elongation complex (SEC). Th1 genes are occupied by H3K4me3 and RNA polymerase II in Th2 cells, while T-bet-mediated recruitment of P-TEFb in Th1 cells activates transcriptional elongation. P-TEFb is recruited to both genes and enhancers, where it activates enhancer RNA transcription...
June 21, 2016: Cell Reports
https://www.readbyqxmd.com/read/27223670/super-elongation-complex-contains-a-tfiif-related-subcomplex
#7
Bruce A Knutson, Marissa L Smith, Nancy Walker-Kopp, Xia Xu
Super elongation complex (SEC) belongs to a family of RNA polymerase II (Pol II) elongation factors that has similar properties as TFIIF, a general transcription factor that increases the transcription elongation rate by reducing pausing. Although SEC has TFIIF-like functional properties, it apparently lacks sequence and structural homology. Using HHpred, we find that SEC contains an evolutionarily related TFIIF-like subcomplex. We show that the SEC subunit ELL interacts with the Pol II Rbp2 subunit, as expected for a TFIIF-like factor...
August 7, 2016: Transcription
https://www.readbyqxmd.com/read/26830226/a-minor-subset-of-super-elongation-complexes-plays-a-predominant-role-in-reversing-hiv-1-latency
#8
Zichong Li, Huasong Lu, Qiang Zhou
Promoter-proximal pausing by RNA polymerase II (Pol II) is a key rate-limiting step in HIV-1 transcription and latency reversal. The viral Tat protein recruits human super elongation complexes (SECs) to paused Pol II to overcome this restriction. Despite the recent progress in understanding the functions of different subsets of SECs in controlling cellular and Tat-activated HIV transcription, little is known about the SEC subtypes that help reverse viral latency in CD4(+) T cells. Here, we used the CRISPR-Cas9 genome-editing tool to knock out the gene encoding the SEC subunit ELL2, AFF1, or AFF4 in Jurkat/2D10 cells, a well-characterized HIV-1 latency model...
April 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/26279188/paf1-a-molecular-regulator-of-promoter-proximal-pausing-by-rna-polymerase-ii
#9
Fei Xavier Chen, Ashley R Woodfin, Alessandro Gardini, Ryan A Rickels, Stacy A Marshall, Edwin R Smith, Ramin Shiekhattar, Ali Shilatifard
The control of promoter-proximal pausing and the release of RNA polymerase II (Pol II) is a widely used mechanism for regulating gene expression in metazoans, especially for genes that respond to environmental and developmental cues. Here, we identify that Pol-II-associated factor 1 (PAF1) possesses an evolutionarily conserved function in metazoans in the regulation of promoter-proximal pausing. Reduction in PAF1 levels leads to an increased release of paused Pol II into gene bodies at thousands of genes. PAF1 depletion results in increased nascent and mature transcripts and increased levels of phosphorylation of Pol II's C-terminal domain on serine 2 (Ser2P)...
August 27, 2015: Cell
https://www.readbyqxmd.com/read/26171280/af4-and-af4n-protein-complexes-recruitment-of-p-tefb-kinase-their-interactome-and-potential-functions
#10
Bastian Scholz, Eric Kowarz, Tanja Rössler, Khalil Ahmad, Dieter Steinhilber, Rolf Marschalek
AF4/AFF1 and AF5/AFF4 are the molecular backbone to assemble "super-elongation complexes" (SECs) that have two main functions: (1) control of transcriptional elongation by recruiting the positive transcription elongation factor b (P-TEFb = CyclinT1/CDK9) that is usually stored in inhibitory 7SK RNPs; (2) binding of different histone methyltransferases, like DOT1L, NSD1 and CARM1. This way, transcribed genes obtain specific histone signatures (e.g. H3K79me2/3, H3K36me2) to generate a transcriptional memory system...
2015: American Journal of Blood Research
https://www.readbyqxmd.com/read/26076193/correction-p-tefb-the-super-elongation-complex-and-mediator-regulate-a-subset-of-non-paused-genes-during-early-drosophila-embryo-development
#11
(no author information available yet)
No abstract text is available yet for this article.
June 2015: PLoS Genetics
https://www.readbyqxmd.com/read/26007649/gene-target-specificity-of-the-super-elongation-complex-sec-family-how-hiv-1-tat-employs-selected-sec-members-to-activate-viral-transcription
#12
Huasong Lu, Zichong Li, Wei Zhang, Ursula Schulze-Gahmen, Yuhua Xue, Qiang Zhou
The AF4/FMR2 proteins AFF1 and AFF4 act as a scaffold to assemble the Super Elongation Complex (SEC) that strongly activates transcriptional elongation of HIV-1 and cellular genes. Although they can dimerize, it is unclear whether the dimers exist and function within a SEC in vivo. Furthermore, it is unknown whether AFF1 and AFF4 function similarly in mediating SEC-dependent activation of diverse genes. Providing answers to these questions, our current study shows that AFF1 and AFF4 reside in separate SECs that display largely distinct gene target specificities...
July 13, 2015: Nucleic Acids Research
https://www.readbyqxmd.com/read/26007630/variants-in-ell2-influencing-immunoglobulin-levels-associate-with-multiple-myeloma
#13
MULTICENTER STUDY
Bhairavi Swaminathan, Guðmar Thorleifsson, Magnus Jöud, Mina Ali, Ellinor Johnsson, Ram Ajore, Patrick Sulem, Britt-Marie Halvarsson, Guðmundur Eyjolfsson, Vilhelmina Haraldsdottir, Christina Hultman, Erik Ingelsson, Sigurður Y Kristinsson, Anna K Kähler, Stig Lenhoff, Gisli Masson, Ulf-Henrik Mellqvist, Robert Månsson, Sven Nelander, Isleifur Olafsson, Olof Sigurðardottir, Hlif Steingrimsdóttir, Annette Vangsted, Ulla Vogel, Anders Waage, Hareth Nahi, Daniel F Gudbjartsson, Thorunn Rafnar, Ingemar Turesson, Urban Gullberg, Kári Stefánsson, Markus Hansson, Unnur Thorsteinsdóttir, Björn Nilsson
Multiple myeloma (MM) is characterized by an uninhibited, clonal growth of plasma cells. While first-degree relatives of patients with MM show an increased risk of MM, the genetic basis of inherited MM susceptibility is incompletely understood. Here we report a genome-wide association study in the Nordic region identifying a novel MM risk locus at ELL2 (rs56219066T; odds ratio (OR)=1.25; P=9.6 × 10(-10)). This gene encodes a stoichiometrically limiting component of the super-elongation complex that drives secretory-specific immunoglobulin mRNA production and transcriptional regulation in plasma cells...
2015: Nature Communications
https://www.readbyqxmd.com/read/25730767/germline-gain-of-function-mutations-in-aff4-cause-a-developmental-syndrome-functionally-linking-the-super-elongation-complex-and-cohesin
#14
Kosuke Izumi, Ryuichiro Nakato, Zhe Zhang, Andrew C Edmondson, Sarah Noon, Matthew C Dulik, Ramakrishnan Rajagopalan, Charles P Venditti, Karen Gripp, Joy Samanich, Elaine H Zackai, Matthew A Deardorff, Dinah Clark, Julian L Allen, Dale Dorsett, Ziva Misulovin, Makiko Komata, Masashige Bando, Maninder Kaur, Yuki Katou, Katsuhiko Shirahige, Ian D Krantz
Transcriptional elongation is critical for gene expression regulation during embryogenesis. The super elongation complex (SEC) governs this process by mobilizing paused RNA polymerase II (RNAP2). Using exome sequencing, we discovered missense mutations in AFF4, a core component of the SEC, in three unrelated probands with a new syndrome that phenotypically overlaps Cornelia de Lange syndrome (CdLS) that we have named CHOPS syndrome (C for cognitive impairment and coarse facies, H for heart defects, O for obesity, P for pulmonary involvement and S for short stature and skeletal dysplasia)...
April 2015: Nature Genetics
https://www.readbyqxmd.com/read/25679530/p-tefb-the-super-elongation-complex-and-mediator-regulate-a-subset-of-non-paused-genes-during-early-drosophila-embryo-development
#15
Olle Dahlberg, Olga Shilkova, Min Tang, Per-Henrik Holmqvist, Mattias Mannervik
Positive Transcription Elongation Factor b (P-TEFb) is a kinase consisting of Cdk9 and Cyclin T that releases RNA Polymerase II (Pol II) into active elongation. It can assemble into a larger Super Elongation Complex (SEC) consisting of additional elongation factors. Here, we use a miRNA-based approach to knock down the maternal contribution of P-TEFb and SEC components in early Drosophila embryos. P-TEFb or SEC depletion results in loss of cells from the embryo posterior and in cellularization defects. Interestingly, the expression of many patterning genes containing promoter-proximal paused Pol II is relatively normal in P-TEFb embryos...
February 2015: PLoS Genetics
https://www.readbyqxmd.com/read/25561469/characterization-of-human-cyclin-dependent-kinase-12-cdk12-and-cdk13-complexes-in-c-terminal-domain-phosphorylation-gene-transcription-and-rna-processing
#16
Kaiwei Liang, Xin Gao, Joshua M Gilmore, Laurence Florens, Michael P Washburn, Edwin Smith, Ali Shilatifard
Cyclin-dependent kinase 9 (CDK9) and CDK12 have each been demonstrated to phosphorylate the RNA polymerase II C-terminal domain (CTD) at serine 2 of the heptad repeat, both in vitro and in vivo. CDK9, as part of P-TEFb and the super elongation complex (SEC), is by far the best characterized of CDK9, CDK12, and CDK13. We employed both in vitro and in vivo assays to further investigate the molecular properties of CDK12 and its paralog CDK13. We isolated Flag-tagged CDK12 and CDK13 and found that they associate with numerous RNA processing factors...
March 2015: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/25201415/integrator-regulates-transcriptional-initiation-and-pause-release-following-activation
#17
Alessandro Gardini, David Baillat, Matteo Cesaroni, Deqing Hu, Jill M Marinis, Eric J Wagner, Mitchell A Lazar, Ali Shilatifard, Ramin Shiekhattar
In unicellular organisms, initiation is the rate-limiting step in transcription; in metazoan organisms, the transition from initiation to productive elongation is also important. Here, we show that the RNA polymerase II (RNAPII)-associated multiprotein complex, Integrator, plays a critical role in both initiation and the release of paused RNAPII at immediate early genes (IEGs) following transcriptional activation by epidermal growth factor (EGF) in human cells. Integrator is recruited to the IEGs in a signal-dependent manner and is required to engage and recruit the super elongation complex (SEC) to EGF-responsive genes to allow release of paused RNAPII and productive transcription elongation...
October 2, 2014: Molecular Cell
https://www.readbyqxmd.com/read/25053741/larp7-suppresses-p-tefb-activity-to-inhibit-breast-cancer-progression-and-metastasis
#18
Xiaodan Ji, Huasong Lu, Qiang Zhou, Kunxin Luo
Transcriptional elongation by RNA polymerase (Pol) II is essential for gene expression during cell growth and differentiation. The positive transcription elongation factor b (P-TEFb) stimulates transcriptional elongation by phosphorylating Pol II and antagonizing negative elongation factors. A reservoir of P-TEFb is sequestered in the inactive 7SK snRNP where 7SK snRNA and the La-related protein LARP7 are required for the integrity of this complex. Here, we show that P-TEFb activity is important for the epithelial-mesenchymal transition (EMT) and breast cancer progression...
July 22, 2014: ELife
https://www.readbyqxmd.com/read/24985467/a-single-point-mutation-in-cyclin-t1-eliminates-binding-to-hexim1-cdk9-and-rna-but-not-to-aff4-and-enforces-repression-of-hiv-transcription
#19
Alona Kuzmina, Nina Verstraete, Sigal Galker, Maayan Maatook, Olivier Bensaude, Ran Taube
BACKGROUND: Human immunodeficiency virus (HIV) gene expression is primarily regulated at the step of transcription elongation. The viral Tat protein recruits the Positive Transcription Elongation Factor b (P-TEFb) and the Super Elongation Complex (SEC) to the HIV promoter and enhances transcription by host RNA polymerase II. RESULTS: To map residues in the cyclin box of cyclin T1 that mediate the binding of P-TEFb to its interacting host partners and support HIV transcription, a pool of N-terminal cyclin T1 mutants was generated...
July 1, 2014: Retrovirology
https://www.readbyqxmd.com/read/24843025/aff4-binding-to-tat-p-tefb-indirectly-stimulates-tar-recognition-of-super-elongation-complexes-at-the-hiv-promoter
#20
Ursula Schulze-Gahmen, Huasong Lu, Qiang Zhou, Tom Alber
Superelongation complexes (SECs) are essential for transcription elongation of many human genes, including the integrated HIV-1 genome. At the HIV-1 promoter, the viral Tat protein binds simultaneously to the nascent TAR RNA and the CycT1 subunit of the P-TEFb kinase in a SEC. To understand the preferential recruitment of SECs by Tat and TAR, we determined the crystal structure of a quaternary complex containing Tat, P-TEFb, and the SEC scaffold, AFF4. Tat and AFF4 fold on the surface of CycT1 and interact directly...
April 24, 2014: ELife
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