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Super elongation complex

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https://www.readbyqxmd.com/read/29026905/imaging-a%C3%AE-1-42-fibril-elongation-reveals-strongly-polarised-growth-and-growth-incompetent-states
#1
Laurence J Young, Gabriele S Kaminski Schierle, Clemens F Kaminski
The major hallmark of Alzheimer's disease is the deposition of plaques of amyloid fibrils formed from amyloid-β (Aβ) peptides. Kinetic studies have contributed significantly towards a mechanistic understanding of amyloid fibril self-assembly, however dynamic features of the aggregation process cannot be captured using ensemble methods. Here we present an assay for imaging Aβ42 aggregation dynamics at the single fibril level, allowing for the quantitative extraction of concentration and temperature dependent kinetic parameters...
October 13, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28985225/disrupting-assembly-of-the-inner-membrane-complex-blocks-plasmodium-falciparum-sexual-stage-development
#2
Molly Parkyn Schneider, Boyin Liu, Philipp Glock, Annika Suttie, Emma McHugh, Dean Andrew, Steven Batinovic, Nicholas Williamson, Eric Hanssen, Paul McMillan, Marion Hliscs, Leann Tilley, Matthew W A Dixon
Transmission of malaria parasites relies on the formation of a specialized blood form called the gametocyte. Gametocytes of the human pathogen, Plasmodium falciparum, adopt a crescent shape. Their dramatic morphogenesis is driven by the assembly of a network of microtubules and an underpinning inner membrane complex (IMC). Using super-resolution optical and electron microscopies we define the ultrastructure of the IMC at different stages of gametocyte development. We characterize two new proteins of the gametocyte IMC, called PhIL1 and PIP1...
October 6, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28955517/aff1-and-aff4-differentially-regulate-the-osteogenic-differentiation-of-human-mscs
#3
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/28878233/a-chalcone-derivative-reactivates-latent-hiv-1-transcription-through-activating-p-tefb-and-promoting-tat-sec-interaction-on-viral-promoter
#4
Jun Wu, Ming-Tao Ao, Rui Shao, Hui-Ru Wang, Diao Yu, Mei-Juan Fang, Xiang Gao, Zhen Wu, Qiang Zhou, Yu-Hua Xue
The principal barrier to the eradication of HIV/AIDS is the existence of latent viral reservoirs. One strategy to overcome this barrier is to use latency-reversing agents (LRAs) to reactivate the latent proviruses, which can then be eliminated by effective anti-retroviral therapy. Although a number of LRAs have been found to reactivate latent HIV, they have not been used clinically due to high toxicity and poor efficacy. In this study, we report the identification of a chalcone analogue called Amt-87 that can significantly reactivate the transcription of latent HIV provirses and act synergistically with known LRAs such as prostratin and JQ1 to reverse latency...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28858629/selective-expression-of-the-transcription-elongation-factor-ell3-in-b-cells-prior-to-ell2-drives-proliferation-and-survival
#5
Lou-Ella M M Alexander, January Watters, Jessica A Reusch, Michelle Maurin, Brook S Nepon-Sixt, Katerina Vrzalikova, Mark G Alexandrow, Paul G Murray, Kenneth L Wright
B cell activation is dependent on a large increase in transcriptional output followed by focused expression on secreted immunoglobulin as the cell transitions to an antibody producing plasma cell. The rapid transcriptional induction is facilitated by the release of poised RNA pol II into productive elongation through assembly of the super elongation complex (SEC). We report that a SEC component, the Eleven -nineteen Lysine-rich leukemia (ELL) family member 3 (ELL3) is dynamically up-regulated in mature and activated human B cells followed by suppression as B cells transition to plasma cells in part mediated by the transcription repressor PRDM1...
August 28, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28747503/identification-of-vaccinia-virus-replisome-and-transcriptome-proteins-by-isolation-of-proteins-on-nascent-dna-coupled-with-mass-spectrometry
#6
Tatiana G Senkevich, George C Katsafanas, Andrea Weisberg, Lisa R Olano, Bernard Moss
Poxviruses replicate within the cytoplasm and encode proteins for DNA and mRNA synthesis. To investigate poxvirus replication and transcription from a new perspective, we incorporated 5-ethynyl-2'-deoxyuridine (EdU) into nascent DNA in cells infected with vaccinia virus (VACV). The EdU-labeled DNA was conjugated to fluor- or biotin-azide and visualized by confocal, superresolution, and transmission electron microscopy. Nuclear labeling decreased dramatically after infection, accompanied by intense labeling of cytoplasmic foci...
October 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28717009/acetylation-on-histone-h3-lysine-9-mediates-a-switch-from-transcription-initiation-to-elongation
#7
Leah A Gates, Jiejun Shi, Aarti D Rohira, Qin Feng, Bokai Zhu, Mark T Bedford, Cari A Sagum, Sung Yun Jung, Jun Qin, Ming-Jer Tsai, Sophia Y Tsai, Wei Li, Charles E Foulds, Bert W O'Malley
The transition from transcription initiation to elongation is a key regulatory step in gene expression, which requires RNA polymerase II (pol II) to escape promoter proximal pausing on chromatin. Although elongation factors promote pause release leading to transcription elongation, the role of epigenetic modifications during this critical transition step is poorly understood. Two histone marks on histone H3, lysine 4 trimethylation (H3K4me3) and lysine 9 acetylation (H3K9ac), co-localize on active gene promoters and are associated with active transcription...
September 1, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28694331/transcriptional-elongation-control-of-hepatitis-b-virus-covalently-closed-circular-dna-transcription-by-super-elongation-complex-and-brd4
#8
Joel Celio Francisco, Qian Dai, Zhuojuan Luo, Yan Wang, Roxanne Hui-Heng Chong, Yee Joo Tan, Wei Xie, Guan-Huei Lee, Chengqi Lin
Chronic hepatitis B virus (HBV) infection can lead to liver cirrhosis and hepatocellular carcinoma. HBV reactivation during or after chemotherapy is a potentially fatal complication for cancer patients with chronic HBV infection. Transcription of HBV is a critical intermediate step of the HBV life cycle. However, factors controlling HBV transcription remain largely unknown. Here, we found that different P-TEFb complexes are involved in the transcription of the HBV viral genome. Both BRD4 and the super elongation complex (SEC) bind to the HBV genome...
October 1, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28677507/the-hiv-1-tat-protein-mechanism-of-action-and-target-for-hiv-1-cure-strategies
#9
Andrew P Rice
The general mechanism involved in Tat activation of RNA Polymerase II (RNAP II) elongation of the integrated HIV-1 was elucidated over 20 years ago. This mechanism involves Tat binding to the TAR RNA element that forms at the 5' end of viral transcripts and recruiting a general RNAP II elongation factor termed as P-TEFb. This elongation factor consists of CDK9 and Cyclin T1, and when recruited by Tat to TAR RNA, CDK9 was proposed to phosphorylate the carboxyl terminal domain of RNAP II and thereby activate elongation...
July 4, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28641539/role-of-host-factors-on-the-regulation-of-tat-mediated-hiv-1-transcription
#10
Guillaume Mousseau, Susana T Valente
BACKGROUND: The viral transactivator Tat protein is a key modulator of HIV-1 replication, as it regulates transcriptional elongation from the integrated proviral genome. Tat recruits the human transcription elongation factor b, and other host proteins, such as the super elongation complex, to activate the cellular RNA polymerase II, normally stalled shortly after transcription initiation at the HIV promoter. By means of a complex set of interactions with host cellular factors, Tat determines the fate of viral activity within the infected cell...
June 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28637181/crosstalk-between-histone-modifications-indicates-that-inhibition-of-arginine-methyltransferase-carm1-activity-reverses-hiv-latency
#11
Zheng Zhang, Bryan C Nikolai, Leah A Gates, Sung Yun Jung, Edward B Siwak, Bin He, Andrew P Rice, Bert W O'Malley, Qin Feng
In eukaryotic cells, the gene expression status is strictly controlled by epigenetic modifications on chromatin. The repressive status of chromatin largely contributes to HIV latency. Studies have shown that modification of histone H3K27 acts as a key molecular switch for activation or suppression of many cellular genes. In this study, we found that K27-acetylated histone H3 specifically recruited Super Elongation Complex (SEC), the transcriptional elongation complex essential for HIV-1 long terminal repeat (LTR)-mediated and general cellular transcription...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28407486/transcriptional-elongation-of-hsv-immediate-early-genes-by-the-super-elongation-complex-drives-lytic-infection-and-reactivation-from-latency
#12
Roberto Alfonso-Dunn, Anne-Marie W Turner, Pierre M Jean Beltran, Jesse H Arbuckle, Hanna G Budayeva, Ileana M Cristea, Thomas M Kristie
The cellular transcriptional coactivator HCF-1 is required for initiation of herpes simplex virus (HSV) lytic infection and for reactivation from latency in sensory neurons. HCF-1 stabilizes the viral Immediate Early (IE) gene enhancer complex and mediates chromatin transitions to promote IE transcription initiation. In infected cells, HCF-1 was also found to be associated with a network of transcription elongation components including the super elongation complex (SEC). IE genes exhibit characteristics of genes controlled by transcriptional elongation, and the SEC-P-TEFb complex is specifically required to drive the levels of productive IE mRNAs...
April 12, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28350987/the-super-elongation-complex-drives-neural-stem-cell-fate-commitment
#13
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/28350981/asymmetric-notch-amplification-to-secure-stem-cell-identity
#14
COMMENT
Anthony M Rossi, Claude Desplan
Stem cells self-renew and produce progenitors with limited proliferative potential. Reporting in Developmental Cell, Liu et al. (2017) demonstrate that in some neural stem cells, Notch activity is asymmetrically amplified by a positive feedback loop with the super elongation complex (SEC) to quickly differentiate between stem cells and progenitors.
March 27, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28340332/super-elongation-complex-promotes-early-hiv-transcription-and-its-function-is-modulated-by-p-tefb
#15
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...
May 27, 2017: Transcription
https://www.readbyqxmd.com/read/28242784/mixed-lineage-leukemia-fusions-and-chromatin-in-leukemia
#16
Andrei V Krivtsov, Takayuki Hoshii, Scott A Armstrong
Recent studies have shown the importance of chromatin-modifying complexes in the maintenance of developmental gene expression and human disease. The mixed lineage leukemia gene (MLL1) encodes a chromatin-modifying protein and was discovered as a result of the cloning of translocations involved in human leukemias. MLL1 is a histone lysine 4 (H3K4) methyltransferase that supports transcription of genes that are important for normal development including homeotic (Hox) genes. MLL1 rearrangements result in expression of fusion proteins without H3K4 methylation activity but may gain the ability to recruit other chromatin-associated complexes such as the H3K79 methyltransferase DOT1L and the super elongation complex...
February 27, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28134250/structural-basis-for-ell2-and-aff4-activation-of-hiv-1-proviral-transcription
#17
Shiqian Qi, Zichong Li, Ursula Schulze-Gahmen, Goran Stjepanovic, Qiang Zhou, James H Hurley
The intrinsically disordered scaffold proteins AFF1/4 and the transcription elongation factors ELL1/2 are core components of the super elongation complex required for HIV-1 proviral transcription. Here we report the 2.0-Å resolution crystal structure of the human ELL2 C-terminal domain bound to its 50-residue binding site on AFF4, the ELLBow. The ELL2 domain has the same arch-shaped fold as the tight junction protein occludin. The ELLBow consists of an N-terminal helix followed by an extended hairpin that we refer to as the elbow joint, and occupies most of the concave surface of ELL2...
January 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/28065413/therapeutic-targeting-of-mll-degradation-pathways-in-mll-rearranged-leukemia
#18
Kaiwei Liang, Andrew G Volk, Jeffrey S Haug, Stacy A Marshall, Ashley R Woodfin, Elizabeth T Bartom, Joshua M Gilmore, Laurence Florens, Michael P Washburn, Kelly D Sullivan, Joaquin M Espinosa, Joseph Cannova, Jiwang Zhang, Edwin R Smith, John D Crispino, Ali Shilatifard
Chromosomal translocations of the mixed-lineage leukemia (MLL) gene with various partner genes result in aggressive leukemia with dismal outcomes. Despite similar expression at the mRNA level from the wild-type and chimeric MLL alleles, the chimeric protein is more stable. We report that UBE2O functions in regulating the stability of wild-type MLL in response to interleukin-1 signaling. Targeting wild-type MLL degradation impedes MLL leukemia cell proliferation, and it downregulates a specific group of target genes of the MLL chimeras and their oncogenic cofactor, the super elongation complex...
January 12, 2017: Cell
https://www.readbyqxmd.com/read/27984731/single-molecule-real-time-3d-imaging-of-the-transcription-cycle-by-modulation-interferometry
#19
Guanshi Wang, Jesse Hauver, Zachary Thomas, Seth A Darst, Alexandros Pertsinidis
Many essential cellular processes, such as gene control, employ elaborate mechanisms involving the coordination of large, multi-component molecular assemblies. Few structural biology tools presently have the combined spatial-temporal resolution and molecular specificity required to capture the movement, conformational changes, and subunit association-dissociation kinetics, three fundamental elements of how such intricate molecular machines work. Here, we report a 3D single-molecule super-resolution imaging study using modulation interferometry and phase-sensitive detection that achieves <2 nm axial localization precision, well below the few-nanometer-sized individual protein components...
December 15, 2016: Cell
https://www.readbyqxmd.com/read/27899651/a-permissive-chromatin-state-regulated-by-zfp281-aff3-in-controlling-the-imprinted-meg3-polycistron
#20
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
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