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Ashlesha Chaubal, Lori A Pile
SIN3 is a global transcriptional coregulator that governs expression of a large repertoire of gene targets. It is an important player in gene regulation, which can repress or activate diverse gene targets in a context-dependent manner. SIN3 is required for several vital biological processes such as cell proliferation, energy metabolism, organ development, and cellular senescence. The functional flexibility of SIN3 arises from its ability to interact with a large variety of partners through protein interaction domains that are conserved across species, ranging from yeast to mammals...
April 17, 2018: Epigenetics & Chromatin
Ande Chennaiah, Yashwant D Vankar
An unprecedented water-mediated and TEMPO-catalyzed, one-step, highly regiospecific and stereoselective functionalization of glycals to 2-azido-2-deoxysugars has been developed using a PIFA-Me3 SiN3 reagent system in the presence of Bu4 NHSO4 as a phase-transfer catalyst. The method is metal-free, proceeds under mild reaction conditions, and tolerates a variety of protecting groups. Using this method, the synthesis of an important trisaccharide unit bound by the monoclonal anti-I Ma antibody has also been demonstrated...
April 17, 2018: Organic Letters
Jingcheng Wang, Yang Tian, Hui Chen, Hui Li, Shusen Zheng
The purpose of the present study was to investigate the underlying molecular mechanism of hepatocellular carcinoma (HCC) using bioinformatics approaches. The microarray dataset GSE64041 was downloaded from the Gene Expression Omnibus database, which included 60 tumor liver samples and 60 matched control samples. Differentially expressed genes (DEGs) between HCC and control groups were identified. Then functional enrichment analyses, protein‑protein interaction (PPI) network, sub‑network and integrated transcription factor (TF)‑microRNA (miRNA)‑target network analyses were performed for these DEGs...
April 12, 2018: Molecular Medicine Reports
Charles A S Banks, Janet L Thornton, Cassandra G Eubanks, Mark K Adams, Sayem Miah, Gina Boanca, Xingyu Liu, Maria Katt, Tari Parmely, Laurence A Florens, Michael P Washburn
Although a variety of affinity purification mass spectrometry (AP-MS) strategies have been used to investigate complex interactions, many of these are susceptible to artifacts due to substantial overexpression of the exogenously expressed bait protein. Here we present a logical and systematic workflow that uses the multifunctional Halo tag to assess the correct localization and behavior of tagged subunits of the Sin3 histone deacetylase complex prior to further AP-MS analysis. Using this workflow, we modified our tagging/expression strategy with 21...
March 29, 2018: Molecular & Cellular Proteomics: MCP
Elizabeth E Palmer, Raman Kumar, Christopher T Gordon, Marie Shaw, Laurence Hubert, Renee Carroll, Marlène Rio, Lucinda Murray, Melanie Leffler, Tracy Dudding-Byth, Myriam Oufadem, Seema R Lalani, Andrea M Lewis, Fan Xia, Allison Tam, Richard Webster, Susan Brammah, Francesca Filippini, John Pollard, Judy Spies, Andre E Minoche, Mark J Cowley, Sarah Risen, Nina N Powell-Hamilton, Jessica E Tusi, LaDonna Immken, Honey Nagakura, Christine Bole-Feysot, Patrick Nitschké, Alexandrine Garrigue, Geneviève de Saint Basile, Emma Kivuva, Richard H Scott, Augusto Rendon, Arnold Munnich, William Newman, Bronwyn Kerr, Claude Besmond, Jill A Rosenfeld, Jeanne Amiel, Michael Field, Jozef Gecz
A recurrent de novo missense variant within the C-terminal Sin3-like domain of ZSWIM6 was previously reported to cause acromelic frontonasal dysostosis (AFND), an autosomal-dominant severe frontonasal and limb malformation syndrome, associated with neurocognitive and motor delay, via a proposed gain-of-function effect. We present detailed phenotypic information on seven unrelated individuals with a recurrent de novo nonsense variant (c.2737C>T [p.Arg913Ter]) in the penultimate exon of ZSWIM6 who have severe-profound intellectual disability and additional central and peripheral nervous system symptoms but an absence of frontonasal or limb malformations...
December 7, 2017: American Journal of Human Genetics
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...
October 24, 2017: Oncotarget
Raj Luxmi, Rashmi Garg, Sudhakar Srivastava, Aniruddha P Sane
The SIN3 family of co-repressors is a family of highly conserved eukaryotic repressor proteins that regulates diverse functions in yeasts and animals but remains largely uncharacterized functionally even in plants like Arabidopsis. The sole SIN3 homologue in banana, MaSIN3, was identified as a 1408 amino acids, nuclear localized protein conserved to other SIN3s in the PAH, HID and HCR domains. Interestingly, MaSIN3 over-expression in Arabidopsis mimics a state of reduced ABA responses throughout plant development affecting growth processes such as germination, root growth, stomatal closure and water loss, flowering and senescence...
November 2017: Plant Science: An International Journal of Experimental Plant Biology
David J Schultz, Penn Muluhngwi, Negin Alizadeh-Rad, Madelyn A Green, Eric C Rouchka, Sabine J Waigel, Carolyn M Klinge
MicroRNAs are biomarkers and potential therapeutic targets for breast cancer. Anacardic acid (AnAc) is a dietary phenolic lipid that inhibits both MCF-7 estrogen receptor α (ERα) positive and MDA-MB-231 triple negative breast cancer (TNBC) cell proliferation with IC50s of 13.5 and 35 μM, respectively. To identify potential mediators of AnAc action in breast cancer, we profiled the genome-wide microRNA transcriptome (microRNAome) in these two cell lines altered by the AnAc 24:1n5 congener. Whole genome expression profiling (RNA-seq) and subsequent network analysis in MetaCore Gene Ontology (GO) algorithm was used to characterize the biological pathways altered by AnAc...
2017: PloS One
Emmanuel C Patin, Selinda Jane Orr, Ulrich E Schaible
The macrophage-inducible C-type lectin (Mincle) is an innate immune receptor on myeloid cells sensing diverse entities including pathogens and damaged cells. Mincle was first described as a receptor for the mycobacterial cell wall glycolipid, trehalose-6,6'-dimycolate, or cord factor, and the mammalian necrotic cell-derived alarmin histone deacetylase complex unit Sin3-associated protein 130. Upon engagement by its ligands, Mincle induces secretion of innate cytokines and other immune mediators modulating inflammation and immunity...
2017: Frontiers in Immunology
Raphaël Pantier, Nicholas P Mullin, Ian Chambers
No abstract text is available yet for this article.
August 1, 2017: EMBO Journal
Kai Schwedtmann, Felix Hennersdorf, Antonio Bauzá, Antonio Frontera, Roland Fischer, Jan J Weigand
The polarized, cationic diphosphene [((Cl) Im(Dipp) )P=P(Dipp)](+) as the triflate salt 7[OTf]((Cl) Im(Dipp) =4,5-dichloro-1,3-bis(Dipp)-imidazol-2-yl; Dipp=2,6-diisopropylphenyl) reacts with azides of type RN3 (R=Dipp or Dmp; Dmp=2,5-dimethylphenyl) in a [2+3] cycloaddition reaction followed by the release of N2 and a subsequent electrocyclic ring-closing reaction to azadiphosphiridine salts [((Cl) Im(Dipp) )P-P(Dipp)-N(R)]10a,b[OTf] (R=Dipp or Dmp). The reaction of 7[X] (X=OTf, GaCl4 ) with the electron-rich azides Me3 SiN3 and NaN3 give the unusual diphosphenimine derivatives [((Cl) Im(Dipp) )P-P(Dipp)=N(SiMe3 )](+) (11[OTf]) and [((Cl) Im(Dipp) )P-P(Dipp)=N(GaCl3 )] (12), respectively, featuring an acyclic P2 N moiety...
May 10, 2017: Angewandte Chemie
Annie Albert Demin, Miju Lee, Chul-Hwan Lee, Yeon-Soo Seo
Lagging strand synthesis is mechanistically far more complicated than leading strand synthesis because it involves multistep processes and requires considerably more enzymes and protein factors. Due to this complexity, multiple fail-safe factors are required to ensure successful replication of the lagging strand DNA. We attempted to identify novel factors that are required in the absence of the helicase activity of Dna2, an essential enzyme in Okazaki-fragment maturation. In this article, we identified Rim11, a GSK-3β-kinase homolog, as a multicopy suppressor of dna2 helicase-dead mutant ( dna2-K1080E )...
June 2017: Genetics
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...
August 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...
January 5, 2017: 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
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