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https://www.readbyqxmd.com/read/29463994/the-homeotic-protein-six3-suppresses-carcinogenesis-and-metastasis-through-recruiting-the-lsd1-nurd-mta3-complex
#1
Yu Zheng, Yi Zeng, Rongfang Qiu, Ruiqiong Liu, Wei Huang, Yongqiang Hou, Shuang Wang, Shuai Leng, Dandan Feng, Yang Yang, Yan Wang
The homeodomain transcription factor SIX3 was recently reported to be a negative regulator of the Wnt pathway and has an emerging role in cancer. However, how SIX3 contributes to tumorigenesis and metastasis is poorly understood. METHODS: We employed affinity purification and mass spectrometry (MS) to identify the proteins physically associated with SIX3. Genome-wide analysis of the SIX3/LSD1/NuRD(MTA3) complex using a chromatin immunoprecipitation-on-chip approach identified a cohort of target genes including WNT1 and FOXC2 , which are critically involved in cell proliferation and epithelial-to-mesenchymal transition...
2018: Theranostics
https://www.readbyqxmd.com/read/29442331/role-of-zic-family-proteins-in-transcriptional-regulation-and-chromatin-remodeling
#2
Minoru Hatayama, Jun Aruga
Proper functions of Zic proteins are essential for animals in health and disease. Here, we summarize our current understanding of the molecular properties and functions of the Zic family across animal species and paralog subtypes. Zics are basic proteins with some posttranslational modifications and can move to the cell nucleus via importin- and CRM1-based nucleocytoplasmic shuttling mechanisms. Degradation is mediated by the ubiquitin proteasome system. Many Zic proteins are capable of binding to two types of target DNA sequences (CTGCTG-core-type and GC-stretch-type)...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29423093/combination-of-a-hypomethylating-agent-and-inhibitors-of-parp-and-hdac-traps-parp1-and-dnmt1-to-chromatin-acetylates-dna-repair-proteins-down-regulates-nurd-and-induces-apoptosis-in-human-leukemia-and-lymphoma-cells
#3
Benigno C Valdez, Yang Li, David Murray, Yan Liu, Yago Nieto, Richard E Champlin, Borje S Andersson
Combination of drugs that target different aspects of aberrant cellular processes is an efficacious treatment for hematological malignancies. Hypomethylating agents (HMAs) and inhibitors of poly(ADP-ribose) polymerases (PARPis) and histone deacetylases (HDACis) are clinically active anti-tumor drugs. We hypothesized that their combination would be synergistically cytotoxic to leukemia and lymphoma cells. Exposure of AML and lymphoma cell lines to the combination of the PARPi niraparib (Npb), the HMA decitabine (DAC) and the HDACi romidepsin (Rom) or panobinostat (Pano) synergistically inhibited cell proliferation by up to 70% via activation of the ATM pathway, increased production of reactive oxygen species, decreased mitochondrial membrane potential, and activated apoptosis...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29370269/the-histone-demethylase-lsd1-regulates-inner-ear-progenitor-differentiation-through-interactions-with-pax2-and-the-nurd-repressor-complex
#4
Dharmeshkumar Patel, Atsushi Shimomura, Sreeparna Majumdar, Matthew C Holley, Eri Hashino
The histone demethylase LSD1 plays a pivotal role in cellular differentiation, particularly in silencing lineage-specific genes. However, little is known about how LSD1 regulates neurosensory differentiation in the inner ear. Here we show that LSD1 interacts directly with the transcription factor Pax2 to form the NuRD co-repressor complex at the Pax2 target gene loci in a mouse otic neuronal progenitor cell line (VOT-N33). VOT-N33 cells expressing a Pax2-response element reporter were GFP-negative when untreated, but became GFP positive after forced differentiation or treatment with a potent LSD inhibitor...
2018: PloS One
https://www.readbyqxmd.com/read/29367758/the-tumor-suppressor-hic1-maintains-chromosomal-stability-independent-of-tp53
#5
Anette Szczepny, Kirstyn Carey, Lisa McKenzie, W Samantha N Jayasekara, Fernando Rossello, Alvaro Gonzalez-Rajal, Andrew S McCaw, Dean Popovski, Die Wang, Anthony J Sadler, Annabelle Mahar, Prudence A Russell, Gavin Wright, Rachael A McCloy, Daniel J Garama, Daniel J Gough, Stephen B Baylin, Andrew Burgess, Jason E Cain, D Neil Watkins
Hypermethylated-in-Cancer 1 (Hic1) is a tumor suppressor gene frequently inactivated by epigenetic silencing and loss-of-heterozygosity in a broad range of cancers. Loss of HIC1, a sequence-specific zinc finger transcriptional repressor, results in deregulation of genes that promote a malignant phenotype in a lineage-specific manner. In particular, upregulation of the HIC1 target gene SIRT1, a histone deacetylase, can promote tumor growth by inactivating TP53. An alternate line of evidence suggests that HIC1 can promote the repair of DNA double strand breaks through an interaction with MTA1, a component of the nucleosome remodeling and deacetylase (NuRD) complex...
January 25, 2018: Oncogene
https://www.readbyqxmd.com/read/29339410/maintenance-of-genome-integrity%C3%A2-by-mi2-homologs-chd-3-and-let-418-in%C3%A2-caenorhabditis-elegans
#6
Carolyn A Turcotte, Solomon A Sloat, Julia A Rigothi, Erika Rosenkranse, Alexandra L Northrup, Nicolas P Andrews, Paula M Checchi
Meiotic recombination depends upon the tightly coordinated regulation of chromosome dynamics and is essential for the production of haploid gametes. Central to this process is the formation and repair of meiotic double-stranded breaks (DSBs), which must take place within the constraints of a specialized chromatin architecture. Here, we demonstrate a role for the nucleosome remodeling and deacetylase (NuRD) complex in orchestrating meiotic chromosome dynamics in Caenorhabditis elegans. Our data reveal that the conserved Mi2 homologs Chromodomain helicase DNA binding protein (CHD-3) and its paralog LET-418 facilitate meiotic progression by ensuring faithful repair of DSBs through homologous recombination...
January 16, 2018: Genetics
https://www.readbyqxmd.com/read/29302954/correction-of-motion-artifacts-in-endoscopic-optical-coherence-tomography-and-autofluorescence-images-based-on-azimuthal-en-face-image-registration
#7
Elham Abouei, Anthony M D Lee, Hamid Pahlevaninezhad, Geoffrey Hohert, Michelle Cua, Pierre Lane, Stephen Lam, Calum MacAulay
We present a method for the correction of motion artifacts present in two- and three-dimensional in vivo endoscopic images produced by rotary-pullback catheters. This method can correct for cardiac/breathing-based motion artifacts and catheter-based motion artifacts such as nonuniform rotational distortion (NURD). This method assumes that en face tissue imaging contains slowly varying structures that are roughly parallel to the pullback axis. The method reduces motion artifacts using a dynamic time warping solution through a cost matrix that measures similarities between adjacent frames in en face images...
January 2018: Journal of Biomedical Optics
https://www.readbyqxmd.com/read/29278858/the-ikaros-family-in-lymphocyte-development
#8
REVIEW
Beate Heizmann, Philippe Kastner, Susan Chan
The IKZF family of transcription factors are essential regulators of lymphopoiesis. Ikaros, Helios, Aiolos and Eos function as transcriptional repressors and activators during T and B cell differentiation and in mature cell function, depending on the stage of development and/or cell type. Their potential mechanisms of action are varied. Ikaros family proteins partner with multiple complexes, including NuRD, PRC2 and transcription elongation factors, to modulate gene expression and the chromatin state. In humans, mutations in the IKZF genes are associated with B cell deficiency, leukemias and autoimmunity...
December 23, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29138280/foxp1-regulation-of-neonatal-vocalizations-via-cortical-development
#9
Noriyoshi Usui, Daniel J Araujo, Ashwinikumar Kulkarni, Marissa Co, Jacob Ellegood, Matthew Harper, Kazuya Toriumi, Jason P Lerch, Genevieve Konopka
The molecular mechanisms driving brain development at risk in autism spectrum disorders (ASDs) remain mostly unknown. Previous studies have implicated the transcription factor FOXP1 in both brain development and ASD pathophysiology. However, the specific molecular pathways both upstream of and downstream from FOXP1 are not fully understood. To elucidate the contribution of FOXP1-mediated signaling to brain development and, in particular, neocortical development, we generated forebrain-specific Foxp1 conditional knockout mice...
November 14, 2017: Genes & Development
https://www.readbyqxmd.com/read/29107595/activation-of-the-aryl-hydrocarbon-receptor-interferes-with-early-embryonic-development
#10
Manolis Gialitakis, Mauro Tolaini, Ying Li, Mercedes Pardo, Lu Yu, Ana Toribio, Jyoti S Choudhary, Kathy Niakan, Venizelos Papayannopoulos, Brigitta Stockinger
The transcriptional program of early embryonic development is tightly regulated by a set of well-defined transcription factors that suppress premature expression of differentiation genes and sustain the pluripotent identity. It is generally accepted that this program can be perturbed by environmental factors such as chemical pollutants; however, the precise molecular mechanisms remain unknown. The aryl hydrocarbon receptor (AHR) is a widely expressed nuclear receptor that senses environmental stimuli and modulates target gene expression...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29063705/refinement-of-the-subunit-interaction-network-within-the-nucleosome-remodelling-and-deacetylase-nurd-complex
#11
Mario Torrado, Jason K K Low, Ana P G Silva, Jason W Schmidberger, Maryam Sana, Mehdi Sharifi Tabar, M Efe Isilak, Courtney S Winning, Cherry Kwong, Max J Bedward, M Jeannette Sperlazza, David C Williams, Nicholas E Shepherd, Joel P Mackay
The nucleosome remodelling and deacetylase (NuRD) complex is essential for the development of complex animals. NuRD has roles in regulating gene expression and repairing damaged DNA. The complex comprises at least six proteins with two or more paralogues of each protein routinely identified when the complex is purified from cell extracts. To understand the structure and function of NuRD, a map of direct subunit interactions is needed. Dozens of published studies have attempted to define direct inter-subunit connectivities...
October 24, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29042910/tumoricidal-activities-of-pterostilbene-depend-upon-destabilizing-the-mta1-nurd-complex-and-enhancing-p53-acetylation-in-hepatocellular-carcinoma
#12
Yu-Yuan Qian, Zhi-Su Liu, Ding-Yu Pan, Kun Li
The present study aimed to assess the tumoricidal effect of metastasis-associated protein 1 (MTA1) induced by pterostilbene (PTER) in hepatocellular carcinoma (HCC). The SMMC-7721 hepatoma cell line was treated with PTER. Following treatment, the mRNA transcript abundance of MTA1 was measured using quantitative polymerase chain reaction. Additionally, cell viability was determined using an MTT assay, and protein expression was measured through western blotting. Cell invasion, motility and apoptosis, as well as the cell cycle, were also investigated...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29042441/transcription-factor-19-interacts-with-histone-3-lysine-4-trimethylation-and-controls-gluconeogenesis-via-the-nucleosome-remodeling-deacetylase-complex
#13
Sabyasachi Sen, Sulagna Sanyal, Dushyant Kumar Srivastava, Dipak Dasgupta, Siddhartha Roy, Chandrima Das
Transcription Factor 19 (TCF19) has been reported as type 1 diabetes associated locus involved in maintenance of pancreatic β cells through a fine-tuned regulation of cell proliferation and apoptosis. TCF19 also exhibits genomic association with type 2 diabetes, although the precise molecular mechanism remains unknown. It harbours both a plant homeodomain (PHD) and a forkhead-associated domain (FHA) implicated in epigenetic recognition and gene regulation, a phenomenon that has remained unexplored. Here, we show that TCF19 selectively interacts with histone 3 lysine 4 trimethylation (H3K4Me3) through its PHD finger...
October 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29020631/covalent-modifications-of-histone-h3k9-promote-binding-of-chd3
#14
Adam H Tencer, Khan L Cox, Luo Di, Joseph B Bridgers, Jie Lyu, Xiaodong Wang, Jennifer K Sims, Tyler M Weaver, Hillary F Allen, Yi Zhang, Jovylyn Gatchalian, Michael A Darcy, Matthew D Gibson, Jinzen Ikebe, Wei Li, Paul A Wade, Jeffrey J Hayes, Brian D Strahl, Hidetoshi Kono, Michael G Poirier, Catherine A Musselman, Tatiana G Kutateladze
Chromatin remodeling is required for genome function and is facilitated by ATP-dependent complexes, such as nucleosome remodeling and deacetylase (NuRD). Among its core components is the chromodomain helicase DNA binding protein 3 (CHD3) whose functional significance is not well established. Here, we show that CHD3 co-localizes with the other NuRD subunits, including HDAC1, near the H3K9ac-enriched promoters of the NuRD target genes. The tandem PHD fingers of CHD3 bind histone H3 tails and posttranslational modifications that increase hydrophobicity of H3K9-methylation or acetylation (H3K9me3 or H3K9ac)-enhance this interaction...
October 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28982760/znf281-enhances-cardiac-reprogramming-by-modulating-cardiac-and-inflammatory-gene-expression
#15
Huanyu Zhou, Maria Gabriela Morales, Hisayuki Hashimoto, Matthew E Dickson, Kunhua Song, Wenduo Ye, Min S Kim, Hanspeter Niederstrasser, Zhaoning Wang, Beibei Chen, Bruce A Posner, Rhonda Bassel-Duby, Eric N Olson
Direct reprogramming of fibroblasts to cardiomyocytes represents a potential means of restoring cardiac function following myocardial injury. AKT1 in the presence of four cardiogenic transcription factors, GATA4, HAND2, MEF2C, and TBX5 (AGHMT), efficiently induces the cardiac gene program in mouse embryonic fibroblasts but not adult fibroblasts. To identify additional regulators of adult cardiac reprogramming, we performed an unbiased screen of transcription factors and cytokines for those that might enhance or suppress the cardiogenic activity of AGHMT in adult mouse fibroblasts...
September 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28977666/chd3-and-chd4-form-distinct-nurd-complexes-with-different-yet-overlapping-functionality
#16
Helen Hoffmeister, Andreas Fuchs, Fabian Erdel, Sophia Pinz, Regina Gröbner-Ferreira, Astrid Bruckmann, Rainer Deutzmann, Uwe Schwartz, Rodrigo Maldonado, Claudia Huber, Anne-Sarah Dendorfer, Karsten Rippe, Gernot Längst
CHD3 and CHD4 (Chromodomain Helicase DNA binding protein), two highly similar representatives of the Mi-2 subfamily of SF2 helicases, are coexpressed in many cell lines and tissues and have been reported to act as the motor subunit of the NuRD complex (nucleosome remodeling and deacetylase activities). Besides CHD proteins, NuRD contains several repressors like HDAC1/2, MTA2/3 and MBD2/3, arguing for a role as a transcriptional repressor. However, the subunit composition varies among cell- and tissue types and physiological conditions...
October 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28963472/zfp296-negatively-regulates-h3k9-methylation-in-embryonic-development-as-a-component-of-heterochromatin
#17
Takumi Matsuura, Satsuki Miyazaki, Tatsushi Miyazaki, Fumi Tashiro, Jun-Ichi Miyazaki
The Cys2/His2-type zinc finger protein Zfp296 has been implicated in stem cell pluripotency and tumor pathogenesis. However, its mechanisms remain elusive. Here, we demonstrated that a Zfp296 deficiency in mice impairs germ-cell development and embryonic growth. Zfp296 was intracellularly localized to heterochromatin in embryos. A GST-Zfp296 pull-down experiment using ES cell nuclear extract followed by LC-MS/MS showed that Zfp296 interacts with component proteins of heterochromatin (such as HP1, Dnmt1, Dnmt3b, and ATRX) and the NuRD complex...
September 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28959722/mta3-regulates-extravillous-trophoblast-invasion-through-nurd-complex
#18
Ying Chen, Sok Kean Khoo, Richard Leach, Kai Wang
Extravillous trophoblast (EVT) invasion is required for remodeling uterine tertiary arteries and placenta development during pregnancy. Compromised EVT invasion may contribute to the pathology of placenta-related diseases. Metastasis -associated protein 3 (MTA3) is one of the subunits of nucleosome remodeling and deacetylation (NuRD) complex that represses transcription in a histone deacetylase-dependent manner. MTA3 is reported to be down-regulated in preeclamptic placentas, suggesting its potential role in EVT invasion...
2017: AIMS Medical Science
https://www.readbyqxmd.com/read/28915537/mta1-expression-in-human-cancers-clinical-and-pharmacological-significance
#19
REVIEW
Vijaya Lakshmi Malisetty, Vasudevarao Penugurti, Prashanth Panta, Suresh Kumar Chitta, Bramanandam Manavathi
Remarkably, majority of the cancer deaths are due to metastasis, not because of primary tumors. Metastasis is one of the important hallmarks of cancer. During metastasis invasion of primary tumor cells from the site of origin to a new organ occurs. Metastasis associated proteins (MTAs) are a small family of transcriptional coregulators that are closely associated with tumor metastasis. These proteins are integral components of nuclear remodeling and deacetylation complex (NuRD). By virtue of being integral components of NuRD, these proteins regulate the gene expression by altering the epigenetic changes such as acetylation and methylation on the target gene chromatin...
November 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28910568/network-of-phosphatases-and-hdac-complexes-at-repressed-chromatin
#20
I J de Castro, H A Amin, V Vinciotti, P Vagnarelli
Tight regulation of gene expression is achieved by a variety of protein complexes that selectively bind chromatin, modify it and change its transcription competency. Histone acetylases (HATs) and deacetylases (HDACs) play an important role in this process. They can generate transcriptionally active or inactive chromatin through the addition (HATs) or removal (HDACs) of acetyl groups on histones, respectively. Repo-Man is a Protein Phosphatase 1 targeting subunit that accumulates on chromosomes during mitotic exit and mediates the removal of mitotic histone H3 phosphorylations...
September 14, 2017: Cell Cycle
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