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https://www.readbyqxmd.com/read/27919072/structure-and-regulation-of-the-chromatin-remodeller-iswi
#1
Lijuan Yan, Li Wang, Yuanyuan Tian, Xian Xia, Zhucheng Chen
ISWI is a member of the SWI2/SNF2 family of chromatin remodellers, which also includes Snf2, Chd1, and Ino80. ISWI is the catalytic subunit of several chromatin remodelling complexes, which mobilize nucleosomes along genomic DNA, promoting replication progression, transcription repression, heterochromatin formation, and many other nuclear processes. The ATPase motor of ISWI is an autonomous remodelling machine, whereas its carboxy (C)-terminal HAND-SAND-SLIDE (HSS) domain functions in binding extranucleosomal linker DNA...
December 5, 2016: Nature
https://www.readbyqxmd.com/read/27804957/ino80-is-required-for-osteogenic-differentiation-of-human-mesenchymal-stem-cells
#2
Chenchen Zhou, Jing Zou, Shujuan Zou, Xiaobing Li
Bone marrow derived human mesenchymal stem cells (MSC) are a great source in bone tissue engineering. However, how to improve the efficiency of MSC osteogenesis remains a big challenge in bone regenerative medicine. Here, we characterized the role of INO80 chromatin remodeling complex in osteogenic differentiation of MSC. We showed that silencing of subunits of INO80 reduced the mineral deposition of MSC in osteogenic condition. Moreover, INO80-silencing MSC cultured in osteogenic condition expressed lower mRNA levels of osteoblast-specific genes, including Runx2, Osx, Col1α1 and OCN...
November 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27779717/mir-148a-inhibits-self-renewal-of-thyroid-cancer-stem-cells-via-repressing-ino80-expression
#3
Weizhong Sheng, Yusheng Chen, Yuda Gong, Tiangeng Dong, Bo Zhang, Weidong Gao
Anaplastic thyroid carcinoma (ATC) is aggressive and lethal with extrathyroidal invasion, distant metastasis, and resistance to conventional therapies. Cancer stem cells (CSCs) are proposed to be responsible for high recurrence rate in ATC. MicroRNAs (miRNAs) have recently been found as an important class of cellular regulators of ATC carcinogenesis. Identification of CSC-related miRNAs and targets is therefore a priority for the development of new therapeutic paradigms. Patient-derived ATC cells were cultured in conditional media on poly-hema-treated dish...
October 25, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27768892/genomic-nucleosome-organization-reconstituted-with-pure-proteins
#4
Nils Krietenstein, Megha Wal, Shinya Watanabe, Bongsoo Park, Craig L Peterson, B Franklin Pugh, Philipp Korber
Chromatin remodelers regulate genes by organizing nucleosomes around promoters, but their individual contributions are obfuscated by the complex in vivo milieu of factor redundancy and indirect effects. Genome-wide reconstitution of promoter nucleosome organization with purified proteins resolves this problem and is therefore a critical goal. Here, we reconstitute four stages of nucleosome architecture using purified components: yeast genomic DNA, histones, sequence-specific Abf1/Reb1, and remodelers RSC, ISW2, INO80, and ISW1a...
October 20, 2016: Cell
https://www.readbyqxmd.com/read/27750218/ino80-promotes-cervical-cancer-tumorigenesis-by-activating-nanog-expression
#5
Jing Hu, Jie Liu, Aozheng Chen, Jia Lyu, Guihai Ai, Qiongjing Zeng, Yi Sun, Chunxia Chen, Jinbo Wang, Jin Qiu, Yi Wu, Jiajing Cheng, Xiujuan Shi, Liwen Song
Ino80 ATPase is an integral component of the INO80 ATP-dependent chromatin-remodeling complex, which regulates transcription, DNA repair and replication. We found that Ino80 was highly expressed in cervical cancer cell lines and tumor samples. Ino80 knockdown inhibited cervical cancer cell proliferation, induced G0/G1 phase cell cycle arrest in vitro and suppressed tumor growth in vivo. However, Ino80 knockdown did not affect cell apoptosis, migration or invasion in vitro. Ino80 overexpression promoted proliferation in the H8 immortalized cervical epithelial cell line, which has low endogenous Ino80 expression as compared to cervical cancer cell lines...
October 14, 2016: Oncotarget
https://www.readbyqxmd.com/read/27692985/monoubiquitination-of-histone-h2b-blocks-eviction-of-histone-variant-h2a-z-from-inducible-enhancers
#6
Gregory Segala, Marcela A Bennesch, Deo Prakash Pandey, Nicolas Hulo, Didier Picard
Covalent modifications of histones play a crucial role in the regulation of gene expression. Histone H2B monoubiquitination has mainly been described as a regulator of transcription elongation, but its role in transcription initiation is poorly documented. We investigated the role of this histone mark (H2Bub1) on different inducible enhancers, in particular those regulated by estrogen receptor α, by loss- and gain-of-function experiments with the specific E3-ubiquitin ligase complex of H2B: RNF20/RNF40. RNF20/RNF40 overexpression causes repression of the induced activity of these enhancers...
October 20, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27641337/ino80-is-required-for-oncogenic-transcription-and-tumor-growth-in-non-small-cell-lung-cancer
#7
S Zhang, B Zhou, L Wang, P Li, B D Bennett, R Snyder, S Garantziotis, D C Fargo, A D Cox, L Chen, G Hu
Epigenetic regulators are attractive targets for the development of new cancer therapies. Among them, the ATP-dependent chromatin remodeling complexes control the chromatin architecture and have important roles in gene regulation. They are often found to be mutated and de-regulated in cancers, but how they influence the cancer gene expression program during cancer initiation and progression is not fully understood. Here we show that the INO80 chromatin remodeling complex is required for oncogenic transcription and tumor growth in non-small-cell lung cancer (NSCLC)...
September 19, 2016: Oncogene
https://www.readbyqxmd.com/read/27535137/human-ino80-yy1-chromatin-remodeling-complex-transcriptionally-regulates-the-brca2-and-cdkn1a-interacting-protein-bccip-in-cells
#8
Jiaming Su, Yi Sui, Jian Ding, Fuqiang Li, Shuang Shen, Yang Yang, Zeming Lu, Fei Wang, Lingling Cao, Xiaoxia Liu, Jingji Jin, Yong Cai
The BCCIP (BRCA2- and CDKN1A-interacting protein) is an important cofactor for BRCA2 in tumor suppression. Although the low expression of BCCIP is observed in multiple clinically diagnosed primary tumor tissues such as ovarian cancer, renal cell carcinoma and colorectal carcinoma, the mechanism of how BCCIP is regulated in cells is still unclear. The human INO80/YY1 chromatin remodeling complex composed of 15 subunits catalyzes ATP-dependent sliding of nucleosomes along DNA. Here, we first report that BCCIP is a novel target gene of the INO80/YY1 complex by presenting a series of experimental evidence...
October 2016: Protein & Cell
https://www.readbyqxmd.com/read/27463665/comment-on-a-histone-acetylation-switch-regulates-h2a-z-deposition-by-the-swr-c-remodeling-enzyme
#9
COMMENT
Feng Wang, Anand Ranjan, Debbie Wei, Carl Wu
Watanabe et al (Reports, 12 April 2013, p. 195) study the yeast SWR1/SWR-C complex responsible for depositing the histone variant H2A.Z by replacing nucleosomal H2A with H2A.Z. They report that reversal of H2A.Z replacement is mediated by SWR1 and related INO80 on an H2A.Z nucleosome carrying H3K56Q. Using multiple assays and reaction conditions, we find no evidence of such reversal of H2A.Z exchange.
July 22, 2016: Science
https://www.readbyqxmd.com/read/27438412/constitutive-turnover-of-histone-h2a-z-at-yeast-promoters-requires-the-preinitiation-complex
#10
Michael Tramantano, Lu Sun, Christy Au, Daniel Labuz, Zhimin Liu, Mindy Chou, Chen Shen, Ed Luk
The assembly of the preinitiation complex (PIC) occurs upstream of the +1 nucleosome which, in yeast, obstructs the transcription start site and is frequently assembled with the histone variant H2A.Z. To understand the contribution of the transcription machinery in the disassembly of the +1 H2A.Z nucleosome, conditional mutants were used to block PIC assembly. A quantitative ChIP-seq approach, which allows detection of global occupancy change, was employed to measure H2A.Z occupancy. Blocking PIC assembly resulted in promoter-specific H2A...
2016: ELife
https://www.readbyqxmd.com/read/27428271/interaction-of-the-chromatin-remodeling-protein-hino80-with-dna
#11
Shweta Mendiratta, Shipra Bhatia, Shruti Jain, Taniya Kaur, Vani Brahmachari
The presence of a highly conserved DNA binding domain in INO80 subfamily predicted that INO80 directly interacts with DNA and we demonstrated its DNA binding activity in vitro. Here we report the consensus motif recognized by the DBINO domain identified by SELEX method and demonstrate the specific interaction of INO80 with the consensus motif. We show that INO80 significantly down regulates the reporter gene expression through its binding motif, and the repression is dependent on the presence of INO80 but not YY1 in the cell...
2016: PloS One
https://www.readbyqxmd.com/read/27352805/distinct-roles-of-the-histone-chaperones-nap1-and-nrp-and-the-chromatin-remodeling-factor-ino80-in-somatic-homologous-recombination-in-arabidopsis-thaliana
#12
Wangbin Zhou, Juan Gao, Jing Ma, Lin Cao, Chi Zhang, Yan Zhu, Aiwu Dong, Wen-Hui Shen
Homologous recombination (HR) of nuclear DNA occurs within the context of a highly complex chromatin structure. Despite extensive studies of HR in diverse organisms, mechanisms regulating HR within the chromatin context remain poorly elucidated. Here we investigate the role and interplay of the histone chaperones NUCLEOSOME ASSEMBLY PROTEIN1 (NAP1) and NAP1-RELATED PROTEIN (NRP) and the ATP-dependent chromatin-remodeling factor INOSITOL AUXOTROPHY80 (INO80) in regulating somatic HR in Arabidopsis thaliana. We show that simultaneous knockout of the four AtNAP1 genes and the two NRP genes in the sextuple mutant m123456-1 barely affects normal plant growth and development...
June 29, 2016: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/27340176/ino80-governs-superenhancer-mediated-oncogenic-transcription-and-tumor-growth-in-melanoma
#13
Bingying Zhou, Li Wang, Shu Zhang, Brian D Bennett, Fan He, Yan Zhang, Chengliang Xiong, Leng Han, Lixia Diao, Pishun Li, David C Fargo, Adrienne D Cox, Guang Hu
Superenhancers (SEs) are large genomic regions with a high density of enhancer marks. In cancer, SEs are found near oncogenes and dictate cancer gene expression. However, how oncogenic SEs are regulated remains poorly understood. Here, we show that INO80, a chromatin remodeling complex, is required for SE-mediated oncogenic transcription and tumor growth in melanoma. The expression of Ino80, the SWI/SNF ATPase, is elevated in melanoma cells and patient melanomas compared with normal melanocytes and benign nevi...
June 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/27269284/nucleosome-disassembly-during-human-non-homologous-end-joining-followed-by-concerted-hira-and-caf-1-dependent-reassembly
#14
Xuan Li, Jessica K Tyler
The cell achieves DNA double-strand break (DSB) repair in the context of chromatin structure. However, the mechanisms used to expose DSBs to the repair machinery and to restore the chromatin organization after repair remain elusive. Here we show that induction of a DSB in human cells causes local nucleosome disassembly, apparently independently from DNA end resection. This efficient removal of histone H3 from the genome during non-homologous end joining was promoted by both ATM and the ATP-dependent nucleosome remodeler INO80...
2016: ELife
https://www.readbyqxmd.com/read/27257055/synergy-and-antagonism-in-regulation-of-recombinant-human-ino80-chromatin-remodeling-complex
#15
Oliver Willhoft, Rohan Bythell-Douglas, Elizabeth A McCormack, Dale B Wigley
We have purified a minimal core human Ino80 complex from recombinant protein expressed in insect cells. The complex comprises one subunit each of an N-terminally truncated Ino80, actin, Arp4, Arp5, Arp8, Ies2 and Ies6, together with a single heterohexamer of the Tip49a and Tip49b proteins. This core complex has nucleosome sliding activity that is similar to that of endogenous human and yeast Ino80 complexes and is also inhibited by inositol hexaphosphate (IP6). We show that IP6 is a non-competitive inhibitor that acts by blocking the stimulatory effect of nucleosomes on the ATPase activity...
September 30, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27112599/architecture-and-nucleotide-dependent-conformational-changes-of-the-rvb1-rvb2-aaa-complex-revealed-by-cryoelectron-microscopy
#16
Caroline A Ewens, Min Su, Liang Zhao, Nardin Nano, Walid A Houry, Daniel R Southworth
Rvb1 and Rvb2 are essential AAA+ proteins that interact together during the assembly and activity of diverse macromolecules including chromatin remodelers INO80 and SWR-C, and ribonucleoprotein complexes including telomerase and snoRNPs. ATP hydrolysis by Rvb1/2 is required for function; however, the mechanism that drives substrate remodeling is unknown. Here we determined the architecture of the yeast Rvb1/2 dodecamer using cryoelectron microscopy and identify that the substrate-binding insertion domain undergoes conformational changes in response to nucleotide state...
May 3, 2016: Structure
https://www.readbyqxmd.com/read/26982580/regulation-of-budding-yeast-cenp-a-levels-prevents-misincorporation-at-promoter-nucleosomes-and-transcriptional-defects
#17
Erica M Hildebrand, Sue Biggins
The exclusive localization of the histone H3 variant CENP-A to centromeres is essential for accurate chromosome segregation. Ubiquitin-mediated proteolysis helps to ensure that CENP-A does not mislocalize to euchromatin, which can lead to genomic instability. Consistent with this, overexpression of the budding yeast CENP-A(Cse4) is lethal in cells lacking Psh1, the E3 ubiquitin ligase that targets CENP-A(Cse4) for degradation. To identify additional mechanisms that prevent CENP-A(Cse4) misincorporation and lethality, we analyzed the genome-wide mislocalization pattern of overexpressed CENP-A(Cse4) in the presence and absence of Psh1 by chromatin immunoprecipitation followed by high throughput sequencing...
March 2016: PLoS Genetics
https://www.readbyqxmd.com/read/26975355/ino80-is-essential-for-proximal-distal-axis-asymmetry-in-part-by-regulating-bmp4-expression
#18
Zhijun Qiu, Zeinab Elsayed, Veronica Peterkin, Suehyb Alkatib, Dorothy Bennett, Joseph W Landry
BACKGROUND: Understanding how embryos specify asymmetric axes is a major focus of biology. While much has been done to discover signaling pathways and transcription factors important for axis specification, comparatively little is known about how epigenetic regulators are involved. Epigenetic regulators operate downstream of signaling pathways and transcription factors to promote nuclear processes, most prominently transcription. To discover novel functions for these complexes in axis establishment during early embryonic development, we characterized phenotypes of a mouse knockout (KO) allele of the chromatin remodeling Ino80 ATPase...
2016: BMC Biology
https://www.readbyqxmd.com/read/26938915/combined-use-of-gene-expression-modeling-and-sirna-screening-identifies-genes-and-pathways-which-enhance-the-activity-of-cisplatin-when-added-at-no-effect-levels-to-non-small-cell-lung-cancer-cells-in-vitro
#19
Ada W Y Leung, Stacy S Hung, Ian Backstrom, Daniel Ricaurte, Brian Kwok, Steven Poon, Steven McKinney, Romulo Segovia, Jenna Rawji, Mohammed A Qadir, Samuel Aparicio, Peter C Stirling, Christian Steidl, Marcel B Bally
Platinum-based combination chemotherapy is the standard treatment for advanced non-small cell lung cancer (NSCLC). While cisplatin is effective, its use is not curative and resistance often emerges. As a consequence of microenvironmental heterogeneity, many tumour cells are exposed to sub-lethal doses of cisplatin. Further, genomic heterogeneity and unique tumor cell sub-populations with reduced sensitivities to cisplatin play a role in its effectiveness within a site of tumor growth. Being exposed to sub-lethal doses will induce changes in gene expression that contribute to the tumour cell's ability to survive and eventually contribute to the selective pressures leading to cisplatin resistance...
2016: PloS One
https://www.readbyqxmd.com/read/26831523/proteomic-and-genomic-analyses-of-the-rvb1-and-rvb2-interaction-network-upon-deletion-of-r2tp-complex-components
#20
Mahadevan Lakshminarasimhan, Gina Boanca, Charles A S Banks, Gaye L Hattem, Ana E Gabriel, Brad D Groppe, Christine Smoyer, Kate E Malanowski, Allison Peak, Laurence Florens, Michael P Washburn
The highly conserved yeast R2TP complex, consisting of Rvb1, Rvb2, Pih1, and Tah1, participates in diverse cellular processes ranging from assembly of protein complexes to apoptosis. Rvb1 and Rvb2 are closely related proteins belonging to the AAA+ superfamily and are essential for cell survival. Although Rvbs have been shown to be associated with various protein complexes including the Ino80 and Swr1chromatin remodeling complexes, we performed a systematic quantitative proteomic analysis of their associated proteins and identified two additional complexes that associate with Rvb1 and Rvb2: the chaperonin-containing T-complex and the 19S regulatory particle of the proteasome complex...
March 2016: Molecular & Cellular Proteomics: MCP
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