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https://www.readbyqxmd.com/read/29786110/multi%C3%A2-layered-prevention-and-treatment-of-chronic-inflammation-organ-fibrosis-and-cancer-associated-with-canonical-wnt-%C3%AE-%C3%A2-catenin-signaling-activation-review
#1
Masaru Katoh
β‑catenin/CTNNB1 is an intracellular scaffold protein that interacts with adhesion molecules (E‑cadherin/CDH1, N‑cadherin/CDH2, VE‑cadherin/CDH5 and α‑catenins), transmembrane‑type mucins (MUC1/CD227 and MUC16/CA125), signaling regulators (APC, AXIN1, AXIN2 and NHERF1/EBP50) and epigenetic or transcriptional regulators (BCL9, BCL9L, CREBBP/CBP, EP300/p300, FOXM1, MED12, SMARCA4/BRG1 and TCF/LEF). Gain‑of‑function CTTNB1 mutations are detected in bladder cancer, colorectal cancer, gastric cancer, liver cancer, lung cancer, pancreatic cancer, prostate cancer and uterine cancer, whereas loss‑of‑function CTNNB1 mutations are also detected in human cancer...
May 17, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29779098/stability-of-chromatin-remodeling-complex-subunits-is-determined-by-their-phosphorylation-status
#2
A M Azieva, A A Sheinov, F A Galkin, S G Georgieva, N V Soshnikova
It was found that, in the differentiated cells of mouse brain, the level of core (Brg1 and BAF155) and specific (BRD7, BAF180, and PHF10) subunits of the chromatin-remodeling complex PBAF is reduced compared to the undifferentiated proliferating cells. Phosphorylation of PBAF complex subunits is required for maintaining their stability in differentiated brain cells.
March 2018: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29765770/persistent-6-oh-bde-47-exposure-impairs-functional-neuronal-maturation-and-alters-expression-of-neurodevelopmentally-relevant-chromatin-remodelers
#3
Robert G Poston, Carissa J Dunn, Pushpita Sarkar, Ramendra N Saha
Polybrominated diphenyl ethers (PBDEs) are a pervasive class of brominated flame retardants that are present in the environment at particularly high levels, especially in the United States. Their environmental stability, propensity for bioaccumulation, and known potential for neurotoxicity has evoked interest regarding their effects on the developing nervous system. Exposure to PBDEs has been strongly associated with neurodevelopmental disorders. However, the details of their mechanistic roles in such disorders are incompletely understood...
January 2018: Environmental Epigenetics
https://www.readbyqxmd.com/read/29750276/thyroid-hormone-receptor-%C3%AE-suppression-of-runx2-is-mediated-by-brahma-related-gene-1-dependent-chromatin-remodeling
#4
Noelle E Gillis, Thomas H Taber, Eric L Bolf, Caitlin M Beaudet, Jennifer A Tomczak, Jeffrey H White, Janet L Stein, Gary S Stein, Jane B Lian, Seth Frietze, Frances E Carr
Thyroid hormone receptor beta (TRβ) suppresses tumor growth through regulation of gene expression, yet the associated TRβ-mediated changes in chromatin assembly are not known. The chromatin ATPase Brahma Related Gene 1 (BRG1, SMARCA4), a key component of chromatin remodeling complexes, is altered in many cancers, but its role in thyroid tumorigenesis and TRβ-mediated gene expression is unknown. We previously identified the oncogene runt-related transcription factor 2 (RUNX2) as a repressive target of TRβ...
May 9, 2018: Endocrinology
https://www.readbyqxmd.com/read/29748386/frequent-irf1-binding-at-remote-elements-without-histone-modification
#5
Mohamed Abou El Hassan, Katherine Huang, Zhaodong Xu, Tao Yu, Rod Bremner
Transcriptional activators bind DNA and recruit cofactors to modify chromatin.  The extent to which these two events are separable is unclear.  Here, using a custom ChIP tiling array to map chromatin modifications, we show that Interferon-γ-induced DNA-binding of signal transducer and activator of transcription 1 (STAT1), typically associated with the transcription factor IFN regulatory factor 1 (IRF1), causes histone acetylation (H3ac, H4ac). In contrast, among IRF1 sites lacking concomitant STAT1 recruitment, only 25% underwent inducible histone acetylation, 31% exhibited constitutive histone acetylation, and 44% had no histone acetylation...
May 10, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29745968/the-long-noncoding-rna-thril-knockdown-protects-hypoxia-induced-injuries-of-h9c2-cells-through-regulating-mir-99a
#6
Jingwen Xia, Nianxin Jiang, Yansong Li, Yong Wei, Xuan Zhang
BACKGROUND: Myocardial infarction (MI) is a leading cause of disease with high morbidity and mortality worldwide. Recent studies have revealed that long non-coding RNAs (lncRNAs) are involved in heart disease pathogenesis. This study aimed to investigate the effect and the molecular basis of THRIL on hypoxia-injured H9C2 cells. METHODS: THRIL, miR-99a and Brahma-related gene 1 (Brg1) expression in H9C2 cells were altered by transient transfections. The cells were subjected to hypoxia for 4 h, and then the levels of THRIL, miR-99a and Brg1 were investigated...
May 10, 2018: Cardiology Journal
https://www.readbyqxmd.com/read/29719619/tp-064-a-potent-and-selective-small-molecule-inhibitor-of-prmt4-for-multiple-myeloma
#7
Kazuhide Nakayama, Magdalena M Szewczyk, Carlo Dela Sena, Hong Wu, Aiping Dong, Hong Zeng, Fengling Li, Renato Ferreira de Freitas, Mohammad S Eram, Matthieu Schapira, Yuji Baba, Mihoko Kunitomo, Douglas R Cary, Michiko Tawada, Akihiro Ohashi, Yasuhiro Imaeda, Kumar Singh Saikatendu, Charles E Grimshaw, Masoud Vedadi, Cheryl H Arrowsmith, Dalia Barsyte-Lovejoy, Atsushi Kiba, Daisuke Tomita, Peter J Brown
Protein arginine methyltransferase (PRMT) 4 (also known as coactivator-associated arginine methyltransferase 1; CARM1) is involved in a variety of biological processes and is considered as a candidate oncogene owing to its overexpression in several types of cancer. Selective PRMT4 inhibitors are useful tools for clarifying the molecular events regulated by PRMT4 and for validating PRMT4 as a therapeutic target. Here, we report the discovery of TP-064, a potent, selective, and cell-active chemical probe of human PRMT4 and its co-crystal structure with PRMT4...
April 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29664021/a-tlr-akt-foxo3-immune-tolerance-like-pathway-disrupts-the-repair-capacity-of-oligodendrocyte-progenitors
#8
Taasin Srivastava, Parham Diba, Justin M Dean, Fatima Banine, Daniel Shaver, Matthew Hagen, Xi Gong, Weiping Su, Ben Emery, Daniel L Marks, Edward N Harris, Bruce Baggenstoss, Paul H Weigel, Larry S Sherman, Stephen A Back
Cerebral white matter injury (WMI) persistently disrupts myelin regeneration by oligodendrocyte progenitor cells (OPCs). We identified a specific bioactive hyaluronan fragment (bHAf) that downregulates myelin gene expression and chronically blocks OPC maturation and myelination via a tolerance-like mechanism that dysregulates pro-myelination signaling via AKT. Desensitization of AKT occurs via TLR4 but not TLR2 or CD44. OPC differentiation was selectively blocked by bHAf in a maturation-dependent fashion at the late OPC (preOL) stage by a noncanonical TLR4/TRIF pathway that induced persistent activation of the FoxO3 transcription factor downstream of AKT...
May 1, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29615549/correlation-of-rs1122608-snp-with-acute-myocardial-infarction-susceptibility-and-clinical-characteristics-in-a-chinese-han-population-a-case-control-study
#9
Quan Fang Chen, Wei Wang, Zhou Huang, Dong Ling Huang, Tian Li, Fan Wang, Jun Li
OBJECTIVE: The correlation of the BRG1 rs1122608 single nucleotide polymorphism (SNP) with acute myocardial infarction (AMI) has been reported in American and European populations. However, whether rs1122608 acts as a protective factor or a risk factor for AMI is controversial. In this study, we aimed to detect the associations between rs1122608 and the clinical characteristics of AMI as well as susceptibility, gene-environment interactions, and risk factors for AMI in a Chinese Han population...
April 2018: Anatolian Journal of Cardiology
https://www.readbyqxmd.com/read/29604291/arid1a-maintains-differentiation-of-pancreatic-ductal-cells-and-inhibits-development-of-pancreatic-ductal-adenocarcinoma-in-mice
#10
Yoshito Kimura, Akihisa Fukuda, Satoshi Ogawa, Takahisa Maruno, Yutaka Takada, Motoyuki Tsuda, Yukiko Hiramatsu, Osamu Araki, Munemasa Nagao, Takaaki Yoshikawa, Kozo Ikuta, Takuto Yoshioka, Zong Wang, Haruhiko Akiyama, Christopher V Wright, Kyoichi Takaori, Shinji Uemoto, Tsutomu Chiba, Hiroshi Seno
BACKGROUND & AIMS: The AT-rich interaction domain 1A gene (ARID1A) encodes a protein that is part of the large ATP-dependent chromatin remodeling complex SWI/SNF and is frequently mutated in human pancreatic ductal adenocarcinomas (PDACs). We investigated the functions of ARID1A during formation of PDACs in mice. METHODS: We performed studies with Ptf1a-Cre; KrasG12D mice, which express activated Kras in the pancreas and develop pancreatic intraepithelial neoplasias (PanINs), as well as those with disruption of Aird1a (Ptf1a-Cre; KrasG12D ; Arid1af/f mice) or disruption of Brg1 (encodes a catalytic ATPase of the SWI/SNF complex) (Ptf1a-Cre; KrasG12D ; Brg1f/f mice)...
March 28, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29590106/tuning-hsf1-levels-drives-distinct-fungal-morphogenetic-programs-with-depletion-impairing-hsp90-function-and-overexpression-expanding-the-target-space
#11
Amanda O Veri, Zhengqiang Miao, Rebecca S Shapiro, Faiza Tebbji, Teresa R O'Meara, Sang Hu Kim, Juan Colazo, Kaeling Tan, Valmik K Vyas, Malcolm Whiteway, Nicole Robbins, Koon Ho Wong, Leah E Cowen
The capacity to respond to temperature fluctuations is critical for microorganisms to survive within mammalian hosts, and temperature modulates virulence traits of diverse pathogens. One key temperature-dependent virulence trait of the fungal pathogen Candida albicans is its ability to transition from yeast to filamentous growth, which is induced by environmental cues at host physiological temperature. A key regulator of temperature-dependent morphogenesis is the molecular chaperone Hsp90, which has complex functional relationships with the transcription factor Hsf1...
March 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29588366/the-long-noncoding-rna-lnczic2-drives-the-self-renewal-of-liver-tumor-initiating-cells-via-the-protein-kinase-c-substrates-marcks-and-marcksl1
#12
Zhenzhen Chen, Yating Liu, Lintong Yao, Shiying Guo, Yanfeng Gao, Pingping Zhu
Liver tumor-initiating cells (TICs) form small subsets of cells in hepatocellular tumors and account for tumorigenesis, metastasis, recurrence, and drug resistance. Recently, we found that the transcription factor Zic family member 2 (ZIC2) is highly expressed in liver TICs and required for their self-renewal. However, the molecular mechanisms underlying self-renewal of liver TICs remains unclear. Here, using expression profiling and CRISPR-interference assays with clinical samples of human liver cancers, we identified a long noncoding RNA (lncRNA), lncZic2, that is located near the ZIC2 locus and was highly expressed in liver cancer and liver TICs...
March 27, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29535420/lncfzd6-initiates-wnt-%C3%AE-catenin-and-liver-tic-self-renewal-through-brg1-mediated-fzd6-transcriptional-activation
#13
Zhenzhen Chen, Yanfeng Gao, Lintong Yao, Yating Liu, Lan Huang, Zhongyi Yan, Wenshan Zhao, Pingping Zhu, Haibo Weng
Liver tumor-initiating cells (TICs), the drivers for liver tumorigenesis, accounts for liver tumor initiation, metastasis, drug resistance and relapse. Wnt/β-catenin signaling pathway emerges as a critical modulator in liver TIC self-renewal. However, the molecular mechanism of Wnt/β-catenin initiation in liver tumorigenesis and liver TICs is still elusive. Here, we examined the expression pattern of 10 Wnt receptors (FZD1-FZD10), and found only FZD6 is overexpressed along with liver tumorigenesis. What's more, a divergent lncRNA of FZD6, termed lncFZD6, is also highly expressed in liver cancer and liver TICs...
March 14, 2018: Oncogene
https://www.readbyqxmd.com/read/29523178/the-bromodomain-containing-protein-ibd1-links-multiple-chromatin-related-protein-complexes-to-highly-expressed-genes-in-tetrahymena-thermophila
#14
Alejandro Saettone, Jyoti Garg, Jean-Philippe Lambert, Syed Nabeel-Shah, Marcelo Ponce, Alyson Burtch, Cristina Thuppu Mudalige, Anne-Claude Gingras, Ronald E Pearlman, Jeffrey Fillingham
BACKGROUND: The chromatin remodelers of the SWI/SNF family are critical transcriptional regulators. Recognition of lysine acetylation through a bromodomain (BRD) component is key to SWI/SNF function; in most eukaryotes, this function is attributed to SNF2/Brg1. RESULTS: Using affinity purification coupled to mass spectrometry (AP-MS) we identified members of a SWI/SNF complex (SWI/SNFTt ) in Tetrahymena thermophila. SWI/SNFTt is composed of 11 proteins, Snf5Tt , Swi1Tt , Swi3Tt , Snf12Tt , Brg1Tt , two proteins with potential chromatin-interacting domains and four proteins without orthologs to SWI/SNF proteins in yeast or mammals...
March 9, 2018: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29521646/incorporating-advances-in-molecular-pathology-into-brain-tumor-diagnostics
#15
José E Velázquez Vega, Daniel J Brat
Recent advances in molecular pathology have reshaped the practice of brain tumor diagnostics. The classification of gliomas has been restructured with the discovery of isocitrate dehydrogenase (IDH) 1/2 mutations in the vast majority of lower grade infiltrating gliomas and secondary glioblastomas (GBM), with IDH-mutant astrocytomas further characterized by TP53 and ATRX mutations. Whole-arm 1p/19q codeletion in conjunction with IDH mutations now define oligodendrogliomas, which are also enriched for CIC, FUBP1, PI3K, NOTCH1, and TERT-p mutations...
May 2018: Advances in Anatomic Pathology
https://www.readbyqxmd.com/read/29520069/an-hdac9-malat1-brg1-complex-mediates-smooth-muscle-dysfunction-in-thoracic-aortic-aneurysm
#16
Christian L Lino Cardenas, Chase W Kessinger, Yisha Cheng, Carolyn MacDonald, Thomas MacGillivray, Brian Ghoshhajra, Luai Huleihel, Saifar Nuri, Ashish S Yeri, Farouc A Jaffer, Naftali Kaminski, Patrick Ellinor, Neal L Weintraub, Rajeev Malhotra, Eric M Isselbacher, Mark E Lindsay
Thoracic aortic aneurysm (TAA) has been associated with mutations affecting members of the TGF-β signaling pathway, or components and regulators of the vascular smooth muscle cell (VSMC) actomyosin cytoskeleton. Although both clinical groups present similar phenotypes, the existence of potential common mechanisms of pathogenesis remain obscure. Here we show that mutations affecting TGF-β signaling and VSMC cytoskeleton both lead to the formation of a ternary complex comprising the histone deacetylase HDAC9, the chromatin-remodeling enzyme BRG1, and the long noncoding RNA MALAT1...
March 8, 2018: Nature Communications
https://www.readbyqxmd.com/read/29485686/hyphal-induction-under-the-condition-without-inoculation-in-candida-albicans-is-triggered-by-brg1-mediated-removal-of-nrg1-inhibition
#17
Chang Su, Jing Yu, Qiangqiang Sun, Qian Liu, Yang Lu
Candida albicans can switch between yeast and hyphae growth forms, which is critical for its pathogenesis. Diluting from saturated cells into fresh medium at 37°C is routinely used to induce hyphae, which depends on the cAMP-PKA pathway-activated transcriptional down-regulation of NRG1 and degradation of Nrg1 protein triggered by inoculation. It is reported that N-acetylglucosamine (GlcNAc), serum or neutral pH could stimulate filamentation in log phase cells, whereas how C. albicans develops hyphae without inoculation remains unknown...
May 2018: Molecular Microbiology
https://www.readbyqxmd.com/read/29482581/the-chromatin-remodeling-subunit-baf200-promotes-normal-hematopoiesis-and-inhibits-leukemogenesis
#18
Lulu Liu, Xiaoling Wan, Peipei Zhou, Xiaoyuan Zhou, Wei Zhang, Xinhui Hui, Xiujie Yuan, Xiaodan Ding, Ruihong Zhu, Guangxun Meng, Hui Xiao, Feng Ma, He Huang, Xianmin Song, Bin Zhou, Sidong Xiong, Yan Zhang
BACKGROUND: Adenosine triphosphate (ATP)-dependent chromatin remodeling SWI/SNF-like BAF and PBAF complexes have been implicated in the regulation of stem cell function and cancers. Several subunits of BAF or PBAF, including BRG1, BAF53a, BAF45a, BAF180, and BAF250a, are known to be involved in hematopoiesis. Baf200, a subunit of PBAF complex, plays a pivotal role in heart morphogenesis and coronary artery angiogenesis. However, little is known on the importance of Baf200 in normal and malignant hematopoiesis...
February 26, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29467221/vascular-development
#19
REVIEW
Mark W Majesky
The vascular system forms as a branching network of endothelial cells that acquire identity as arterial, venous, hemogenic, or lymphatic. Endothelial specification depends on gene targets transcribed by Ets domain-containing factors, including Ets variant gene 2 (Etv2), together with the activity of chromatin-remodeling complexes containing Brahma-related gene-1 (Brg1). Once specified and assembled into vessels, mechanisms regulating lumen diameter and axial growth ensure that the structure of the branching vascular network matches the need for perfusion of target tissues...
March 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29463646/mutant-isocitrate-dehydrogenase-1-disrupts-pkm2-%C3%AE-catenin-brg1-transcriptional-network-driven-cd47-expression
#20
Pruthvi Gowda, Shruti Patrick, Ankita Singh, Touseef Sheikh, Ellora Sen
A gain-of-function mutation in isocitrate dehydrogenase 1 (IDH1) affects immune surveillance in gliomas. As elevated CD47 levels are associated with immune evasion in cancers, its status in gliomas harboring mutant IDH1 (IDH1-MT cells) was investigated. Decreased CD47 expression in IDH1-R132H-overexpressing cells was accompanied by diminished nuclear β-catenin, pyruvate kinase isoform M2 (PKM2), and TCF4 levels compared to those in cells harboring wild-type IDH1 (IDH1-WT cells). The inhibition of β-catenin in IDH1-WT cells abrogated CD47 expression, β-catenin-TCF4 interaction, and the transactivational activity of β-catenin/TCF4...
May 1, 2018: Molecular and Cellular Biology
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