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Debasish Halder, Chang-Hee Lee, Ji Young Hyun, Gyeong-Eon Chang, Eunji Cheong, Injae Shin
Sin3 is a transcriptional corepressor for REST silencing machinery that represses multiple neuronal genes in non-neuronal cells. However, functions of Sin3 (Sin3A and Sin3B) in suppression of neuronal phenotypes are not well characterized. Herein we show that Sin3A knockdown impedes the repressive activity of REST and enhances differentiation of pluripotent P19 cells into electrophysiologically active neurons without inducing astrogenesis. It is also found that silencing Sin3B induces neurogenesis of P19 cells with a lower efficiency than Sin3A knockdown...
March 17, 2017: Scientific Reports
Mihaela E Sardiu, Joshua M Gilmore, Brad Groppe, Laurence Florens, Michael P Washburn
Biological networks consist of functional modules, however detecting and characterizing such modules in networks remains challenging. Perturbing networks is one strategy for identifying modules. Here we used an advanced mathematical approach named topological data analysis (TDA) to interrogate two perturbed networks. In one, we disrupted the S. cerevisiae INO80 protein interaction network by isolating complexes after protein complex components were deleted from the genome. In the second, we reanalyzed previously published data demonstrating the disruption of the human Sin3 network with a histone deacetylase inhibitor...
March 8, 2017: Scientific Reports
Felix Kliewe, Maike Engelhardt, Rasha Aref, Hans-Joachim Schüller
It is generally assumed that pathway-specific transcriptional activators recruit pleiotropic coactivators (such as chromatin-modifying complexes or general transcription factors), while specific repressors contact pleiotropic corepressors creating an inaccessible chromatin by the action of histone deacetylases. We have previously shown that the negative regulator Opi1 of yeast phospholipid biosynthesis inhibits transcription by recruiting corepressors Sin3 and Cyc8 in the presence of precursor molecules inositol and choline...
February 7, 2017: Current Genetics
Mengying Liu, Lori A Pile
Chromatin modification and cellular metabolism are tightly connected. Chromatin modifiers regulate the expression of genes involved in metabolism and, in turn, the levels of metabolites. The generated metabolites are utilized by chromatin modifiers to affect epigenetic modification. The mechanism for this cross-talk, however, remains incompletely understood. The corepressor SIN3 controls histone acetylation through association with the histone deacetylase RPD3. The SIN3 complex is known to regulate genes involved in a number of metabolic processes...
February 3, 2017: Journal of Biological Chemistry
Johannes A Baus, Felix M Mück, Heidi Schneider, Reinhold Tacke
Reaction of the donor-stabilized silylene [iPrNC(NiPr2 )NiPr]2 Si (1) with FeBr2 , CoBr2 , NiBr2 ⋅MeOCH2 CH2 OMe, ZnCl2 , and ZnBr2 afforded the respective transition-metal silylene complexes 4-8, the formation of which can be described in terms of a Lewis acid/base reaction (4, 5, 7, 8) or a nucleophilic substitution reaction (6). However, the reactivity profile of silylene 1 is not only based on its strong Lewis base character; the different coordination modes of the two guanidinato ligands (4-6 vs. 7 and 8) add an additional reactivity facet...
November 22, 2016: Chemistry: a European Journal
Zhi Wang, Fengying Chen, Xiaoying Li, Hong Cao, Meng Ding, Cun Zhang, Jinghong Zuo, Chaonan Xu, Jimei Xu, Xin Deng, Yong Xiang, Wim J J Soppe, Yongxiu Liu
Histone acetylation is known to affect the speed of seed germination, but the molecular regulatory basis of this remains ambiguous. Here we report that loss of function of two histone deacetylase-binding factors, SWI-INDEPENDENT3 (SIN3)-LIKE1 (SNL1) and SNL2, results in accelerated radicle protrusion and growth during seed germination. AUXIN RESISTANT 1 (AUX1) is identified as a key factor in this process, enhancing germination speed downstream of SNL1 and SNL2. AUX1 expression and histone H3 acetylation at lysines 9 and 18 is regulated by SNL1 and SNL2...
November 11, 2016: Nature Communications
David J Cantor, Gregory David
Hematopoietic stem cells (HSCs) reside at the top of the hematopoietic hierarchy and are the origin of all blood cells produced throughout an individual's life. The balance between HSC self-renewal and differentiation is maintained by various intrinsic and extrinsic mechanisms. Among these, the molecular pathways that restrict cell cycle progression are critical to the maintenance of functional HSCs. Alterations in the regulation of cell cycle progression in HSCs invariably lead to the development of hematologic malignancies or bone marrow failure syndromes...
January 5, 2017: Blood
Monica J Lewis, Jianzhong Liu, Emily Falk Libby, Minnkyong Lee, Nigel P S Crawford, Douglas R Hurst
SIN3 corepressor complexes play important roles in both normal development and breast cancer. Mammalian cells have two paralogs of SIN3 (SIN3A and SIN3B) that are encoded by distinct genes and have unique functions in many developmental processes. However, specific roles for SIN3A and SIN3B in breast cancer progression have not been characterized. We generated stable knockdown cells of SIN3 paralogs individually and in combination using three non-overlapping shRNA. Stable knockdown of SIN3B caused a significant decrease in transwell invasion through Matrigel and decreased the number of invasive colonies when grown in a 3D extracellular matrix...
November 29, 2016: Oncotarget
Felix Kliewe, Jacqueline Kumme, Mathias Grigat, Stefan Hintze, Hans-Joachim Schüller
Structural genes of phospholipid biosynthesis in the yeast Saccharomyces cerevisiae are transcribed when precursor molecules inositol and choline (IC) are limiting. Gene expression is stimulated by the heterodimeric activator Ino2/Ino4, which binds to ICRE (inositol/choline-responsive element) promoter sequences. Activation is prevented by repressor Opi1, counteracting Ino2 when high concentrations of IC are available. Here we show that ICRE-dependent gene activation is repressed not only by an excess of IC but also under conditions of phosphate starvation...
October 15, 2016: Yeast
Piyush Deokar, Monica Vasiliu, David A Dixon, Karl O Christe, Ralf Haiges
The binary zirconium and hafnium polyazides [PPh4 ]2 [M(N3 )6 ] (M=Zr, Hf) were obtained in near quantitative yields from the corresponding metal fluorides MF4 by fluoride-azide exchange reactions with Me3 SiN3 in the presence of two equivalents of [PPh4 ][N3 ]. The novel polyazido compounds were characterized by their vibrational spectra and their X-ray crystal structures. Both anion structures provide experimental evidence for near-linear M-N-N coordination of metal azides. The species [M(N3 )4 ], [M(N3 )5 ](-) and [M(N3 )6 ](2-) (M=Ti, Zr, Hf) were studied by quantum chemical calculations at the electronic structure density functional theory and MP2 levels...
October 13, 2016: Angewandte Chemie
Kaori Terasaki, Sydney I Ramirez, Shinji Makino
Rift Valley fever virus (RVFV), a member of the genus Phlebovirus within the family Bunyaviridae, causes periodic outbreaks in livestocks and humans in countries of the African continent and Middle East. RVFV NSs protein, a nonstructural protein, is a major virulence factor that exhibits several important biological properties. These include suppression of general transcription, inhibition of IFN-β promoter induction and degradation of double-stranded RNA-dependent protein kinase R. Although each of these biological functions of NSs are considered important for countering the antiviral response in the host, the individual contributions of these functions towards RVFV virulence remains unclear...
October 2016: PLoS Neglected Tropical Diseases
D R Welch, C A Manton, D R Hurst
Metastasis requires coordinated expression of multiple genetic cassettes, often via epigenetic regulation of gene transcription. BRMS1 blocks metastasis, but not orthotopic tumor growth in multiple tumor types, presumably via SIN3 chromatin remodeling complexes. Although there is an abundance of strong data supporting BRMS1 as a metastasis suppressor, the mechanistic data directly connecting molecular pathways with inhibition of particular steps in metastasis are not well defined. In this review, the data for BRMS1-mediated metastasis suppression in multiple tumor types are discussed along with the steps in metastasis that are inhibited...
2016: Advances in Cancer Research
Martin Hermus, Aria Mansouri Tehrani, Jakoah Brgoch
A structural instability in the orthorhombic carbonitridosilicate La2Si4N6C arises when calculating the ab initio phonon dispersion curves. The presence of imaginary modes indicates the compound reported in space group Pnma is dynamically unstable with the eigenvectors showing a monoclinic distortion pathway leading to space group P21/c. Synthesizing La2Si4N6C using a high-temperature route and conducting a co-refinement with high-resolution synchrotron X-ray and neutron powder diffraction shows the predicted peak splitting confirming the predicted lower symmetry crystal structure...
September 19, 2016: Inorganic Chemistry
Yeon-Jin Kwon, Boris A Leibovitch, Nidhi Bansal, Lutecia Pereira, Chi-Yeh Chung, Edgardo V Ariztia, Arthur Zelent, Eduardo F Farias, Samuel Waxman
Cancer cell invasion is an obligatory step for metastatic dissemination that contributes to rapid relapse and a poorer survival in triple negative breast cancer (TNBC) patients. Development of novel therapeutic strategies to block tumor invasion is an unmet need in the treatment of cancer. We reported that the selective inhibition of the PAH2 domain of SIN3A protein function markedly suppressed metastatic dissemination to the lungs in TNBC xenograft bearing mice. Here, we show that TNBC cell lines treated with Sin3 interaction domain (SID) decoy peptides that bind to PAH2 display a strong in vitro inhibition of transwell invasion...
August 19, 2016: Oncotarget
Tianyi Zhang, Zhentao Sheng, Wei Du
Inactivation of HDAC1 and its homolog HDAC2 or addition of HDAC inhibitors in mammalian systems induces apoptosis, cell cycle arrest, and developmental defects. Although these phenotypes have been extensively characterized, the precise underlying mechanisms remain unclear, particularly in in vivo settings. In this study, we show that inactivation of Rpd3, the only HDAC1 and HDAC2 ortholog in Drosophila, induced apoptosis and clone elimination in the developing eye and wing imaginal discs. Depletion of Rpd3 by RNAi cell-autonomously increased JNK activities and decreased activities of Yki, the nuclear effecter of Hippo signaling pathway...
August 2016: Mechanisms of Development
Nidhi Bansal, Almudena Bosch, Boris Leibovitch, Lutecia Pereira, Elena Cubedo, Jianshi Yu, Keely Pierzchalski, Jace W Jones, Melissa Fishel, Maureen Kane, Arthur Zelent, Samuel Waxman, Eduardo Farias
Triple negative breast cancer (TNBC) frequently relapses locally, regionally or as systemic metastases. Development of targeted therapy that offers significant survival benefit in TNBC is an unmet clinical need. We have previously reported that blocking interactions between PAH2 domain of chromatin regulator Sin3A and the Sin3 interaction domain (SID) containing proteins by SID decoys result in EMT reversal, and re-expression of genes associated with differentiation. Here we report a novel and therapeutically relevant combinatorial use of SID decoys...
July 12, 2016: Oncotarget
Yanfang Ye, Lucy Kirkham-McCarthy, Robert S Lahue
Trinucleotide repeats (TNRs) are tandem arrays of three nucleotides that can expand in length to cause at least 17 inherited human diseases. Somatic expansions in patients can occur in differentiated tissues where DNA replication is limited and cannot be a primary source of somatic mutation. Instead, mouse models of TNR diseases have shown that both inherited and somatic expansions can be suppressed by the loss of certain DNA repair factors. It is generally believed that these repair factors cause misprocessing of TNRs, leading to expansions...
July 2016: DNA Repair
Ashlesha Chaubal, Sokol V Todi, Lori A Pile
SIN3 is a transcriptional corepressor that acts as a scaffold for a histone deacetylase (HDAC) complex. The SIN3 complex regulates various biological processes, including organ development, cell proliferation, and energy metabolism. Little is known, however, about the regulation of SIN3 itself. There are two major isoforms of Drosophila SIN3, 187 and 220, which are differentially expressed. Intrigued by the developmentally timed exchange of SIN3 isoforms, we examined whether SIN3 187 controls the fate of the 220 counterpart...
May 27, 2016: Journal of Biological Chemistry
N Bansal, G David, E Farias, S Waxman
Revolutionizing treatment strategies is an urgent clinical need in the fight against cancer. Recently the scientific community has recognized chromatin-associated proteins as promising therapeutic candidates. However, there is a need to develop more targeted epigenetic inhibitors with less toxicity. Sin3 family is one such target which consists of evolutionary conserved proteins with two paralogues Sin3A and Sin3B. Sin3A/B are global transcription regulators that provide a versatile platform for diverse chromatin-modifying activities...
2016: Advances in Cancer Research
C S Lyu, Y L Zhang, J H Lang
OBJECTIVE: To investigate the efficiency of biological function of AT rich interaction domain 1A (ARID1A) gene silenced by small interfering RNA (siRNA) on ovarian clear cell carcinoma ES2 cell line. METHODS: (1) The three pairs ARID1A gene siRNA interference fragments siN1 (ARID1A-705), siN2 (ARID1A-1513), siN3 (ARID1A-2282) and one pair negative control were respectively designed, and transfected into ES2 cells by RNA interference max reagent transiently. Reverse transcription (RT)-PCR and western blot methods were used to detect the expression of ARID1A mRNA and protein in ES2 cells transfected with interference fragments respectively...
March 2016: Zhonghua Fu Chan Ke za Zhi
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