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https://www.readbyqxmd.com/read/29759113/distinct-roles-of-atm-and-atr-in-the-regulation-of-arp8-phosphorylation-to-prevent-chromosome-translocations
#1
Jiying Sun, Lin Shi, Aiko Kinomura, Atsuhiko Fukuto, Yasunori Horikoshi, Yukako Oma, Masahiko Harata, Masae Ikura, Tsuyoshi Ikura, Roland Kanaar, Satoshi Tashiro
Chromosomal translocations are hallmarks of various types of cancers and leukemias. However, the molecular mechanisms of chromosome translocations remain largely unknown. The ataxia-telangiectasia mutated (ATM) protein, a DNA damage signaling regulator, facilitates DNA repair to prevent chromosome abnormalities. Previously, we showed that ATM deficiency led to the 11q23 chromosome translocation, the most frequent chromosome abnormalities in secondary leukemia. Here, we show that ARP8, a subunit of the INO80 chromatin remodeling complex, is phosphorylated after etoposide treatment...
May 8, 2018: ELife
https://www.readbyqxmd.com/read/29750421/genome-wide-analysis-of-lncrnas-in-3-untranslated-regions-cr933609-acts-as-a-decoy-to-protect-the-ino80d-gene
#2
Chun-Chi Chang, Ting-Yuan Liu, Ya-Ting Lee, Yu-Chia Chen, Kun-Tu Yeh, Chien-Chin Lee, Ya-Ling Chen, Pei-Chin Lin, Ya-Sian Chang, Wen-Ling Chan, Ta-Chih Liu, Jan-Gowth Chang
Long non‑coding RNAs (lncRNAs) have various functions, including chromatin remodeling and the regulation of gene expression at the transcriptional and post-transcriptional levels. However, few lncRNAs have been investigated comprehensively, with the majority being uncharacterized. In the present study, a bioinformatics pipeline was established to identify novel lncRNA sequences similar to the 3'-untranslated regions (3'‑UTRs) of protein-coding genes. These pairs of lncRNAs and coding genes contained the same microRNA (miRNA) target sites; the lncRNA CR933609 matched the 3'‑UTR of INO80 complex subunit D (INO80D) mRNA...
May 8, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29664398/the-nucleosomal-acidic-patch-relieves-auto-inhibition-by-the-iswi-remodeler-snf2h
#3
Nathan Gamarra, Stephanie L Johnson, Michael J Trnka, Alma L Burlingame, Geeta J Narlikar
ISWI family chromatin remodeling motors use sophisticated autoinhibition mechanisms to control nucleosome sliding. Yet how the different autoinhibitory domains are regulated is not well understood. Here we show that an acidic patch formed by histones H2A and H2B of the nucleosome relieves the autoinhibition imposed by the AutoN and the NegC regions of the human ISWI remodeler SNF2h. Further, by single molecule FRET we show that the acidic patch helps control the distance travelled per translocation event. We propose a model in which the acidic patch activates SNF2h by providing a landing pad for the NegC and AutoN auto-inhibitory domains...
April 17, 2018: ELife
https://www.readbyqxmd.com/read/29653123/long-noncoding-rna-lnchand2-promotes-liver-repopulation-via-c-met-signaling
#4
Yanying Wang, Pingping Zhu, Jing Wang, Xiaoxiao Zhu, Jianjun Luo, Shu Meng, Jiayi Wu, Buqing Ye, Luyun He, Ying Du, Lei He, Runsheng Chen, Yong Tian, Zusen Fan
BACKGROUND & AIMS: Long noncoding RNAs (lncRNAs) play important roles in various biological processes and regulate gene expression by diverse mechanisms. However, how lncRNAs regulate liver repopulation is unknown. METHODS: Here we identify a divergent lncRNA termed LncHand2 that is highly expressed over liver regeneration after partial hepatectomy (PHx). RESULTS: LncHand2 is constitutively expressed in the nuclei of pericentral hepatocytes in mouse and human livers...
April 10, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29643509/structural-basis-for-atp-dependent-chromatin-remodelling-by-the-ino80-complex
#5
Sebastian Eustermann, Kevin Schall, Dirk Kostrewa, Kristina Lakomek, Mike Strauss, Manuela Moldt, Karl-Peter Hopfner
In the eukaryotic nucleus, DNA is packaged in the form of nucleosomes, each of which comprises about 147 base pairs of DNA wrapped around a histone protein octamer. The position and histone composition of nucleosomes is governed by ATP-dependent chromatin remodellers1-3 such as the 15-subunit INO80 complex 4 . INO80 regulates gene expression, DNA repair and replication by sliding nucleosomes, the exchange of histone H2A.Z with H2A, and the positioning of + 1 and -1 nucleosomes at promoter DNA5-8 . The structures and mechanisms of these remodelling reactions are currently unknown...
April 11, 2018: Nature
https://www.readbyqxmd.com/read/29643506/structure-and-regulation-of-the-human-ino80-nucleosome-complex
#6
Rafael Ayala, Oliver Willhoft, Ricardo J Aramayo, Martin Wilkinson, Elizabeth A McCormack, Lorraine Ocloo, Dale B Wigley, Xiaodong Zhang
Access to DNA within nucleosomes is required for a variety of processes in cells including transcription, replication and repair. Consequently, cells encode multiple systems that remodel nucleosomes. These complexes can be simple, involving one or a few protein subunits, or more complicated multi-subunit machines 1 . Biochemical studies2-4 have placed the motor domains of several chromatin remodellers in the superhelical location 2 region of the nucleosome. Structural studies of yeast Chd1 and Snf2-a subunit in the complex with the capacity to remodel the structure of chromatin (RSC)-in complex with nucleosomes5-7 have provided insights into the basic mechanism of nucleosome sliding performed by these complexes...
April 11, 2018: Nature
https://www.readbyqxmd.com/read/29567837/the-brd3-et-domain-recognizes-a-short-peptide-motif-through-a-mechanism-that-is-conserved-across-chromatin-remodelers-and-transcriptional-regulators
#7
Dorothy C Wai, Taylor N Szyszka, Amy E Campbell, Cherry Kwong, Lorna E Wilkinson-White, Ana P G Silva, Jason K K Low, Ann H Kwan, Roland Gamsjaeger, James N Chalmers, Wayne M Patrick, Bin Lu, Christopher R Vakoc, Gerd A Blobel, Joel P Mackay
Members of the bromodomain and extra-terminal domain (BET) family of proteins (bromodomain-containing (BRD) 2, 3, 4 and T) are widely expressed and highly conserved regulators of gene expression in eukaryotes. These proteins have been intimately linked to human disease and more than a dozen clinical trials are currently underway to test BET-protein inhibitors as modulators of cancer therapies. However, although it is clear that these proteins use their bromodomains to bind both histones and transcription factors bearing acetylated lysine residues, the molecular mechanisms by which BET-family proteins regulate gene expression are not well defined...
March 22, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29561707/lncrna-ptcsc3-affects-drug-resistance-of-anaplastic-thyroid-cancer-through-stat3-ino80-pathway
#8
Xiao-Ming Wang, Yang Liu, Yu-Xia Fan, Zheng Liu, Qing-Ling Yuan, Meng Jia, Geng Zu-Shi, Ling Gu, Xiu-Bo Lu
Background LncRNA PTCSC3 is a tumor suppressor in thyroid cancer, and its role in drug resistance of anaplastic thyroid cancer (ATC) to chemotherapy drug doxorubicin was investigated in this study. Methods Expression of RNA and protein was analyzed by qRT-PCR and western blot, respectively. Flow cytometry was used to analyze the expression rate of CD133+ cells. The endogenous expression of related genes was modulated by recombinant plasmids and cell transfection. Combination condition and interaction between PTCSC3 and STAT3 were determined by RIP and RNA pull-down assay, respectively...
March 21, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29462149/the-ino80-chromatin-remodeler-sustains-metabolic-stability-by-promoting-tor-signaling-and-regulating-histone-acetylation
#9
Sean L Beckwith, Erin K Schwartz, Pablo E García-Nieto, Devin A King, Graeme J Gowans, Ka Man Wong, Tessa L Eckley, Alexander P Paraschuk, Egan L Peltan, Laura R Lee, Wei Yao, Ashby J Morrison
Chromatin remodeling complexes are essential for gene expression programs that coordinate cell function with metabolic status. However, how these remodelers are integrated in metabolic stability pathways is not well known. Here, we report an expansive genetic screen with chromatin remodelers and metabolic regulators in Saccharomyces cerevisiae. We found that, unlike the SWR1 remodeler, the INO80 chromatin remodeling complex is composed of multiple distinct functional subunit modules. We identified a strikingly divergent genetic signature for the Ies6 subunit module that links the INO80 complex to metabolic homeostasis...
February 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29452642/the-yeast-ino80-complex-operates-as-a-tunable-dna-length-sensitive-switch-to-regulate-nucleosome-sliding
#10
Coral Y Zhou, Stephanie L Johnson, Laura J Lee, Adam D Longhurst, Sean L Beckwith, Matthew J Johnson, Ashby J Morrison, Geeta J Narlikar
The yeast INO80 chromatin remodeling complex plays essential roles in regulating DNA damage repair, replication, and promoter architecture. INO80's role in these processes is likely related to its ability to slide nucleosomes, but the underlying mechanism is poorly understood. Here we use ensemble and single-molecule enzymology to study INO80-catalyzed nucleosome sliding. We find that the rate of nucleosome sliding by INO80 increases ∼100-fold when the flanking DNA length is increased from 40 to 60 bp. Furthermore, once sliding is initiated, INO80 moves the nucleosome rapidly at least 20 bp without pausing to re-assess flanking DNA length, and it can change the direction of nucleosome sliding without dissociation...
February 15, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29432129/identification-of-two-distinct-classes-of-the-human-ino80-complex-genome-wide
#11
John S Runge, Jesse R Raab, Terry Magnuson
Chromatin remodeling and histone modifying enzymes play a critical role in shaping the regulatory output of a cell. Although much is known about these classes of proteins, identifying the mechanisms by which they coordinate gene expression programs remains an exciting topic of investigation. One factor that may contribute to the targeting and activity of chromatin regulators is local chromatin landscape. We leveraged genomic approaches and publically-available datasets to characterize the chromatin landscape at targets of the human INO80 chromatin remodeling complex (INO80-C)...
March 28, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29383140/ino80-haploinsufficiency-inhibits-colon-cancer-tumorigenesis-via-replication-stress-induced-apoptosis
#12
Shin-Ai Lee, Han-Sae Lee, Shin-Kyoung Hur, Sang Won Kang, Goo Taeg Oh, Daekee Lee, Jongbum Kwon
The INO80 chromatin-remodeling complex performs functions in many chromosomal processes that are crucial for genome stability, such as DNA replication and stalled replication fork recovery. Although these functions suggest that INO80 acts as a tumor suppressor, its specific role in tumorigenesis has remained obscure. Here, we show that a haploinsufficient mutation of Ino80, the catalytic ATPase of the INO80 complex, decreased intestinal adenomatous polyps and increased survival in an Apcmin/+ mouse model of colon cancer...
December 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29372961/-coactivator-complexes-participate-in-different-stages-of-the-drosophila-melanogaster-hsp70-gene-transcription
#13
M Yu Mazina, P K Derevyanko, E V Kocheryzhkina, Yu V Nikolenko, A N Krasnov, N E Vorobyeva
The objective of this study was to identify transcriptional coactivators participating in transcription elongation of the hsp70 gene induced by heat shock. We found that all investigated coactivator complexes participate in transcription of this gene, as significant level of them were present at the gene promoter in its active state. For most of the coactivators (except for p300/CBP, Set2, and Mediator complex), we also observed a considerable increase of their binding level at the coding region of the gene after activation of its transcription by heat shock...
February 2017: Genetika
https://www.readbyqxmd.com/read/29371594/endothelial-deletion-of-ino80-disrupts-coronary-angiogenesis-and-causes-congenital-heart-disease
#14
Siyeon Rhee, Jae I Chung, Devin A King, Gaetano D'amato, David T Paik, Anna Duan, Andrew Chang, Danielle Nagelberg, Bikram Sharma, Youngtae Jeong, Maximilian Diehn, Joseph C Wu, Ashby J Morrison, Kristy Red-Horse
During development, the formation of a mature, well-functioning heart requires transformation of the ventricular wall from a loose trabecular network into a dense compact myocardium at mid-gestation. Failure to compact is associated in humans with congenital diseases such as left ventricular non-compaction (LVNC). The mechanisms regulating myocardial compaction are however still poorly understood. Here, we show that deletion of the Ino80 chromatin remodeler in vascular endothelial cells prevents ventricular compaction in the developing mouse heart...
January 25, 2018: Nature Communications
https://www.readbyqxmd.com/read/29346761/ino80-chromatin-remodeling-coordinates-metabolic-homeostasis-with-cell-division
#15
Graeme J Gowans, Alicia N Schep, Ka Man Wong, Devin A King, William J Greenleaf, Ashby J Morrison
Adaptive survival requires the coordination of nutrient availability with expenditure of cellular resources. For example, in nutrient-limited environments, 50% of all S. cerevisiae genes synchronize and exhibit periodic bursts of expression in coordination with respiration and cell division in the yeast metabolic cycle (YMC). Despite the importance of metabolic and proliferative synchrony, the majority of YMC regulators are currently unknown. Here, we demonstrate that the INO80 chromatin-remodeling complex is required to coordinate respiration and cell division with periodic gene expression...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29323271/cryo-em-structures-of-the-human-ino80-chromatin-remodeling-complex
#16
Ricardo J Aramayo, Oliver Willhoft, Rafael Ayala, Rohan Bythell-Douglas, Dale B Wigley, Xiaodong Zhang
Access to chromatin for processes such as transcription and DNA repair requires the sliding of nucleosomes along DNA. This process is aided by chromatin-remodeling complexes, such as the multisubunit INO80 chromatin-remodeling complex. Here we present cryo-EM structures of the active core complex of human INO80 at 9.6 Å, with portions at 4.1-Å resolution, and reconstructions of combinations of subunits. Together, these structures reveal the architecture of the INO80 complex, including Ino80 and actin-related proteins, which is assembled around a single RUVBL1 (Tip49a) and RUVBL2 (Tip49b) AAA+ heterohexamer...
January 2018: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28988953/meddling-with-fate-the-proteasomal-deubiquitinating-enzymes
#17
REVIEW
Stefanie A H de Poot, Geng Tian, Daniel Finley
Three deubiquitinating enzymes-Rpn11, Usp14, and Uch37-are associated with the proteasome regulatory particle. These enzymes allow proteasomes to remove ubiquitin from substrates before they are translocated into the core particle to be degraded. Although the translocation channel is too narrow for folded proteins, the force of translocation unfolds them mechanically. As translocation proceeds, ubiquitin chains bound to substrate are drawn to the channel's entry port, where they can impede further translocation...
November 10, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28904333/the-ino80-complex-mediates-epigenetic-centromere-propagation-via-active-removal-of-histone-h3
#18
Eun Shik Choi, Youngseo Cheon, Keunsoo Kang, Daeyoup Lee
The centromere is the chromosomal locus at which the kinetochore is assembled to direct chromosome segregation. The histone H3 variant, centromere protein A (CENP-A), is known to epigenetically mark active centromeres, but the mechanism by which CENP-A propagates at the centromere, replacing histone H3, remains poorly understood. Using fission yeast, here we show that the Ino80 adenosine triphosphate (ATP)-dependent chromatin-remodeling complex, which removes histone H3-containing nucleosomes from associated chromatin, promotes CENP-ACnp1 chromatin assembly at the centromere in a redundant manner with another chromatin-remodeling factor Chd1Hrp1 ...
September 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28884116/the-role-of-pontin-and-reptin-in-cellular-physiology-and-cancer-etiology
#19
REVIEW
Yu-Qian Mao, Walid A Houry
Pontin (RUVBL1, TIP49, TIP49a, Rvb1) and Reptin (RUVBL2, TIP48, TIP49b, Rvb2) are highly conserved ATPases of the AAA+ (ATPases Associated with various cellular Activities) superfamily and are involved in various cellular processes that are important for oncogenesis. First identified as being upregulated in hepatocellular carcinoma and colorectal cancer, their overexpression has since been shown in multiple cancer types such as breast, lung, gastric, esophageal, pancreatic, kidney, bladder as well as lymphatic, and leukemic cancers...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28735899/mot1-ino80c-and-nc2-function-coordinately-to-regulate-pervasive-transcription-in-yeast-and-mammals
#20
Yong Xue, Suman K Pradhan, Fei Sun, Constantinos Chronis, Nancy Tran, Trent Su, Christopher Van, Ajay Vashisht, James Wohlschlegel, Craig L Peterson, H T Marc Timmers, Siavash K Kurdistani, Michael F Carey
Pervasive transcription initiates from cryptic promoters and is observed in eukaryotes ranging from yeast to mammals. The Set2-Rpd3 regulatory system prevents cryptic promoter function within expressed genes. However, conserved systems that control pervasive transcription within intergenic regions have not been well established. Here we show that Mot1, Ino80 chromatin remodeling complex (Ino80C), and NC2 co-localize on chromatin and coordinately suppress pervasive transcription in S. cerevisiae and murine embryonic stem cells (mESCs)...
August 17, 2017: Molecular Cell
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