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https://www.readbyqxmd.com/read/28179136/expression-purification-and-characterization-of-the-human-mta2-rbbp7-complex
#1
Christoffer Brasen, Jerzy Dorosz, Anders Wiuf, Thomas Boesen, Osman Mirza, Michael Gajhede
The repressive Nucleosome Remodeling and histone Deacetylation (NuRD) complex remodels the chromatin structure by coupling ATP-dependent remodeling activity with histone deacetylase function and plays important roles in regulating gene transcription, DNA damage repair and chromatin assembly. The complex is composed of six subunits: Metastasis Associated proteins MTA1/2/3 initially recruit histone chaperones RBBP4/7 followed by the histone deacetylases HDAC1/2 forming a core complex. Further association of the CpG-binding protein MBD2/3, p66α/β and the ATP-dependent helicase CDH3/4 constitutes the NuRD complex...
February 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28099864/satb1-expression-governs-epigenetic-repression-of-pd-1-in-tumor-reactive-t-cells
#2
Tom L Stephen, Kyle K Payne, Ricardo A Chaurio, Michael J Allegrezza, Hengrui Zhu, Jairo Perez-Sanz, Alfredo Perales-Puchalt, Jenny M Nguyen, Ana E Vara-Ailor, Evgeniy B Eruslanov, Mark E Borowsky, Rugang Zhang, Terri M Laufer, Jose R Conejo-Garcia
Despite the importance of programmed cell death-1 (PD-1) in inhibiting T cell effector activity, the mechanisms regulating its expression remain poorly defined. We found that the chromatin organizer special AT-rich sequence-binding protein-1 (Satb1) restrains PD-1 expression induced upon T cell activation by recruiting a nucleosome remodeling deacetylase (NuRD) complex to Pdcd1 regulatory regions. Satb1 deficienct T cells exhibited a 40-fold increase in PD-1 expression. Tumor-derived transforming growth factor β (Tgf-β) decreased Satb1 expression through binding of Smad proteins to the Satb1 promoter...
January 17, 2017: Immunity
https://www.readbyqxmd.com/read/28094816/methylation-specific-targeting-of-a-chromatin-remodeling-complex-from-sponges-to-humans
#3
Jason M Cramer, Deborah Pohlmann, Fernando Gomez, Leslie Mark, Benjamin Kornegay, Chelsea Hall, Edhriz Siraliev-Perez, Ninad M Walavalkar, M Jeannette Sperlazza, Stephanie Bilinovich, Jeremy W Prokop, April L Hill, David C Williams
DNA cytosine methylation and methyl-cytosine binding domain (MBD) containing proteins are found throughout all vertebrate species studied to date. However, both the presence of DNA methylation and pattern of methylation varies among invertebrate species. Invertebrates generally have only a single MBD protein, MBD2/3, that does not always contain appropriate residues for selectively binding methylated DNA. Therefore, we sought to determine whether sponges, one of the most ancient extant metazoan lineages, possess an MBD2/3 capable of recognizing methylated DNA and recruiting the associated nucleosome remodeling and deacetylase (NuRD) complex...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28088556/regulation-of-docetaxel-sensitivity-in-prostate-cancer-cells-by-hsa-mir-125a-3p-via-modulation-of-mta1-signaling
#4
Jian-Zhou Liu, Feng-Yan Yin, Chang-You Yan, Hui Wang, Xiao-Hui Luo
OBJECTIVE: To identify the potential down-stream targets of hsa-miR-125a-3p, a mature form of miR-125a, during the pathogenesis of chemoresistance in prostate cancer (PCa). METHODS: Expression levels of hsa-miR-125a-3p was assessed in chemoresistant PCa tissues and experimentally-established chemoresistant cells using quantitative RT-PCR (qRT-PCR). The effect of hsa-miR-125a-3p knockdown or hsa-miR-125a-3p overexpression on the Dox-induced cell death was evaluated using apoptosis ELISA in chemosensitive PC-3 cells or in chemoresistant PC-3 cells (PC-3R)...
January 11, 2017: Urology
https://www.readbyqxmd.com/read/28053041/lhx2-interacts-with-the-nurd-complex-and-regulates-cortical-neuron-subtype-determinants-fezf2-and-sox11
#5
Bhavana Muralidharan, Zeba Khatri, Upasana Maheshwari, Ritika Gupta, Basabdatta Roy, Saurabh J Pradhan, Krishanpal Karmodiya, Hari Padmanabhan, Ashwin S Shetty, Chinthapalli Balaji, Ullas Kolthur-Seetharam, Jeffrey D Macklis, Sanjeev Galande, Shubha Tole
: In the developing cerebral cortex, sequential transcriptional programs take neuroepithelial cells from proliferating progenitors to differentiated neurons with unique molecular identities. The regulatory changes that occur in the chromatin of the progenitors are not well understood. During deep layer neurogenesis, we show that transcription factor LHX2 binds to distal regulatory elements of Fezf2 and Sox11, critical determinants of neuron subtype identity in the mouse neocortex. We demonstrate that LHX2 binds to the nucleosome remodeling and histone deacetylase histone remodeling complex subunits LSD1, HDAC2, and RBBP4, which are proximal regulators of the epigenetic state of chromatin...
January 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28007841/a-network-of-chromatin-factors-is-regulating-the-transition-to-postembryonic-development-in-caenorhabditis-elegans
#6
Peter Erdelyi, Xing Wang, Marina Suleski, Chantal Wicky
Mi2 proteins are evolutionarily conserved, ATP-dependent chromatin remodelers of the CHD family that play key roles in stem cell differentiation and reprogramming. In Caenorhabditis elegans, the let-418 gene encodes one of the two Mi2 homologs, which is part of at least two chromatin complexes, namely the Nucleosome Remodeling and histone Deacetylase (NuRD) complex and the MEC complex, and functions in larval development, vulval morphogenesis, lifespan regulation, and cell fate determination. To explore the mechanisms involved in the action of LET-418/Mi2, we performed a genome-wide RNA interference (RNAi) screen for suppressors of early larval arrest associated with let-418 mutations...
February 9, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/27935866/hic1-hypermethylated-in-cancer-1-sumoylation-is-dispensable-for-dna-repair-but-is-essential-for-the-apoptotic-dna-damage-response-ddr-to-irreparable-dna-double-strand-breaks-dsbs
#7
Sonia Paget, Marion Dubuissez, Vanessa Dehennaut, Joe Nassour, Brennan T Harmon, Nathalie Spruyt, Ingrid Loison, Corinne Abbadie, Brian R Rood, Dominique Leprince
The tumor suppressor gene HIC1 (Hypermethylated In Cancer 1) encodes a transcriptional repressor mediating the p53-dependent apoptotic response to irreparable DNA double-strand breaks (DSBs) through direct transcriptional repression of SIRT1. HIC1 is also essential for DSB repair as silencing of endogenous HIC1 in BJ-hTERT fibroblasts significantly delays DNA repair in functional Comet assays. HIC1 SUMOylation favours its interaction with MTA1, a component of NuRD complexes. In contrast with irreparable DSBs induced by 16-hours of etoposide treatment, we show that repairable DSBs induced by 1 h etoposide treatment do not increase HIC1 SUMOylation or its interaction with MTA1...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/27909100/lhx2-interacts-with-the-nurd-complex-and-regulates-cortical-neuron-subtype-determinants-fezf2-and-sox11
#8
Bhavana Muralidharan, Zeba Khatri, Upasana Maheshwari, Ritika Gupta, Basabdatta Roy, Saurabh J Pradhan, Krishanpal Karmodiya, Hari Padmanabhan, Ashwin Shetty, Chinthapalli Balaji, Ullas Kolthur-Seetharam, Jeffrey D Macklis, Sanjeev Galande, Shubha Tole
: In the developing cerebral cortex, sequential transcriptional programs take neuroepithelial cells from proliferating progenitors to differentiated neurons with unique molecular identities. The regulatory changes that occur in the chromatin of the progenitors are not well understood. During deep layer neurogenesis, we show that transcription factor Lhx2 binds to distal regulatory elements of Fezf2 and Sox11, critical determinants of neuron subtype identity in the mouse neocortex. We demonstrate that Lhx2 binds to the NuRD histone remodeling complex subunits LSD1, HDAC2, and RBBP4, which are proximal regulators of the epigenetic state of chromatin...
December 1, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27894081/mbd3-inhibits-formation-of-liver-cancer-stem-cells
#9
Ruizhi Li, Qihua He, Shuo Han, Mingzhi Zhang, Jinwen Liu, Ming Su, Shiruo Wei, Xuan Wang, Li Shen
Liver cancer cells can be reprogrammed into induced cancer stem cells (iCSCs) by exogenous expression of the reprogramming transcription factors Oct4, Sox2, Klf4 and c-Myc (OSKM). The nucleosome remodeling and deacetylase (NuRD) complex is essential for reprogramming somatic cells. In this study, we investigated the function of NuRD in the induction of liver CSCs. We showed that suppression of methyl-CpG binding domain protein 3 (MBD3), a core subunit of the NuRD repressor complex, together with OSKM transduction, induces conversion of liver cancer cells into stem-like cells...
January 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/27806305/a-functional-switch-of-nurd-chromatin-remodeling-complex-subunits-regulates-mouse-cortical-development
#10
Justyna Nitarska, Jacob G Smith, William T Sherlock, Michele M G Hillege, Alexi Nott, William D Barshop, Ajay A Vashisht, James A Wohlschlegel, Richard Mitter, Antonella Riccio
Histone modifications and chromatin remodeling represent universal mechanisms by which cells adapt their transcriptional response to rapidly changing environmental conditions. Extensive chromatin remodeling takes place during neuronal development, allowing the transition of pluripotent cells into differentiated neurons. Here, we report that the NuRD complex, which couples ATP-dependent chromatin remodeling with histone deacetylase activity, regulates mouse brain development. Subunit exchange of CHDs, the core ATPase subunits of the NuRD complex, is required for distinct aspects of cortical development...
November 1, 2016: Cell Reports
https://www.readbyqxmd.com/read/27793668/zip-restores-estrogen-receptor-expression-and-response-to-tamoxifen-in-estrogen-receptor-negative-tumors
#11
Ning Zhu, Jing Zhang, Xiaodong Qin, Ruidong Miao, Yuping Du, Jinbo Yang
As a component of NURD histone deacetylase complex, ZIP serves as a tumor suppressor gene in the development of breast tumors. However, whether it takes part in chemotherapy resistance remains poorly defined. In the present study, we reported that ZIP enhanced the response to SERM chemotherapy in ER-negative cells. Overexpression of ZIP suppressed EGFR expression level and restored ERalpha protein level in cells resistant to Tamoxifen. In vivo data confirmed those in vitro findings.
October 25, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27773593/foxk2-elicits-massive-transcription-repression-and-suppresses-the-hypoxic-response-and-breast-cancer-carcinogenesis
#12
Lin Shan, Xing Zhou, Xinhua Liu, Yue Wang, Dongxue Su, Yongqiang Hou, Na Yu, Chao Yang, Beibei Liu, Jie Gao, Yang Duan, Jianguo Yang, Wanjin Li, Jing Liang, Luyang Sun, Kexin Chen, Chenghao Xuan, Lei Shi, Yan Wang, Yongfeng Shang
Although clinically associated with severe developmental defects, the biological function of FOXK2 remains poorly explored. Here we report that FOXK2 interacts with transcription corepressor complexes NCoR/SMRT, SIN3A, NuRD, and REST/CoREST to repress a cohort of genes including HIF1β and EZH2 and to regulate several signaling pathways including the hypoxic response. We show that FOXK2 inhibits the proliferation and invasion of breast cancer cells and suppresses the growth and metastasis of breast cancer. Interestingly, FOXK2 is transactivated by ERα and transrepressed via reciprocal successive feedback by HIF1β/EZH2...
November 14, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27732854/zmynd8-co-localizes-with-nurd-on-target-genes-and-regulates-poly-adp-ribose-dependent-recruitment-of-gatad2a-nurd-to-sites-of-dna-damage
#13
Cornelia G Spruijt, Martijn S Luijsterburg, Roberta Menafra, Rik G H Lindeboom, Pascal W T C Jansen, Raghu Ram Edupuganti, Marijke P Baltissen, Wouter W Wiegant, Moritz C Voelker-Albert, Filomena Matarese, Anneloes Mensinga, Ina Poser, Harmjan R Vos, Hendrik G Stunnenberg, Haico van Attikum, Michiel Vermeulen
NuRD (nucleosome remodeling and histone deacetylase) is a versatile multi-protein complex with roles in transcription regulation and the DNA damage response. Here, we show that ZMYND8 bridges NuRD to a number of putative DNA-binding zinc finger proteins. The MYND domain of ZMYND8 directly interacts with PPPLΦ motifs in the NuRD subunit GATAD2A. Both GATAD2A and GATAD2B exclusively form homodimers and define mutually exclusive NuRD subcomplexes. ZMYND8 and NuRD share a large number of genome-wide binding sites, mostly active promoters and enhancers...
October 11, 2016: Cell Reports
https://www.readbyqxmd.com/read/27673553/regulated-and-functional-expression-of-the-corepressor-mta3-in-rodent-testis
#14
Ke He, Hu Qu, Hui Wang, Shun Zhang, Xin-Hong Qian, Wei Li
Metastasis-associated protein 3 (MTA3) is a subunit of the Mi-2/nucleosome remodeling and deacetylase (NuRD) protein complex, with relevant roles in the regulation of cancerous epithelial to mesenchymal transition (ETM) in an estrogen-dependent manner, recently involved in the modulation of different physiological processes. Although these findings connect MTA3 expression with hormonal signaling in various systems, little is known about whether this relationship is conserved in testis where hormonal action is intensive...
September 27, 2016: Endocrinology
https://www.readbyqxmd.com/read/27650712/mbd3-expression-and-dna-binding-patterns-are-altered-in-a-rat-model-of-temporal-lobe-epilepsy
#15
Joanna Bednarczyk, Konrad J Dębski, Anna M Bot, Katarzyna Lukasiuk
The aim of the present study was to examine involvement of MBD3 (methyl-CpG-binding domain protein 3), a protein involved in reading DNA methylation patterns, in epileptogenesis and epilepsy. We used a well-characterized rat model of temporal lobe epilepsy that is triggered by status epilepticus, evoked by electrical stimulation of the amygdala. Stimulated and sham-operated animals were sacrificed 14 days after stimulation. We found that MBD3 transcript was present in neurons, oligodendrocytes, and astrocytes in both control and epileptic animals...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27633282/pathogenesis-of-b%C3%A3-rjeson-forssman-lehmann-syndrome-insights-from-phf6-function
#16
REVIEW
Arezu Jahani-Asl, Cheng Cheng, Chi Zhang, Azad Bonni
Intellectual disability encompasses a large set of neurodevelopmental disorders of cognition that are more common in males than females. Although mutations in over 100 X-linked genes associated to intellectual disability have been identified, only a few X-linked intellectual disability proteins have been intensively studied. Hence, the molecular mechanisms underlying the majority of X-linked intellectual disability disorders remain poorly understood. A substantial fraction of X-linked intellectual disability genes encode nuclear proteins, suggesting that elucidating their functions in the regulation of transcription may provide novel insights into the pathogenesis of intellectual disability...
December 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27606067/the-nurd-complex-component-p66-suppresses-photoreceptor-neuron-regeneration-in-planarians
#17
Constanza Vásquez-Doorman, Christian P Petersen
Regeneration involves precise control of cell fate to produce an appropriate complement of tissues formed within a blastema. Several chromatin-modifying complexes have been identified as required for regeneration in planarians, but it is unclear whether this class of molecules uniformly promotes the production of differentiated cells. We identify a function for p66, encoding a DNA-binding protein component of the NuRD (nucleosome remodeling and deacetylase) complex, as well as the chromodomain helicase chd4, in suppressing production of photoreceptor neurons (PRNs) in planarians...
June 2016: Regeneration
https://www.readbyqxmd.com/read/27603575/repression-of-neuronal-nitric-oxide-nnos-synthesis-by-mta1-is-involved-in-oxidative-stress-induced-neuronal-damage
#18
Zi-Jun Gao, Jie Min, Xu-Cai Wu, Tian Yang, Chang-You Yan, Bu-Huai Dong, Tao Zhang
The Metastasis-associated protein 1 (MTA1) coregulator, an essential component of the nucleosome remodeling and deacetylase (NuRD) complex, potentiates neuroprotective effects against ischemia/reperfusion (I/R) injury. But the underlying mechanism(s) remain largely unknown. Here, we discovered that neuronal MTA1 was a target of oxidative stress, and stimulation of neurons with oxygen glucose deprivation (OGD) treatment significantly inhibited MTA1 expression. Additionally, MTA1 depletion augmented ischemic oxidative stress and thus promoted oxidative stress-induced neuronal cell death by OGD...
October 7, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27570688/circumferential-optical-coherence-tomography-angiography-imaging-of-the-swine-esophagus-using-a-micromotor-balloon-catheter
#19
Hsiang-Chieh Lee, Osman Oguz Ahsen, Kaicheng Liang, Zhao Wang, Cody Cleveland, Lucas Booth, Benjamin Potsaid, Vijaysekhar Jayaraman, Alex E Cable, Hiroshi Mashimo, Robert Langer, Giovanni Traverso, James G Fujimoto
We demonstrate a micromotor balloon imaging catheter for ultrahigh speed endoscopic optical coherence tomography (OCT) which provides wide area, circumferential structural and angiographic imaging of the esophagus without contrast agents. Using a 1310 nm MEMS tunable wavelength swept VCSEL light source, the system has a 1.2 MHz A-scan rate and ~8.5 µm axial resolution in tissue. The micromotor balloon catheter enables circumferential imaging of the esophagus at 240 frames per second (fps) with a ~30 µm (FWHM) spot size...
August 1, 2016: Biomedical Optics Express
https://www.readbyqxmd.com/read/27524420/twist1-promotes-breast-cancer-invasion-and-metastasis-by-silencing-foxa1-expression
#20
Y Xu, L Qin, T Sun, H Wu, T He, Z Yang, Q Mo, L Liao, J Xu
The heterogeneous breast cancers can be classified into different subtypes according to their histopathological characteristics and molecular signatures. Foxa1 expression is linked with luminal breast cancer (LBC) with good prognosis, whereas Twist1 expression is associated with basal-like breast cancer (BLBC) with poor prognosis owing to its role in promoting epithelial-to-mesenchymal transition (EMT), invasiveness and metastasis. However, the regulatory and functional relationships between Twist1 and Foxa1 in breast cancer progression are unknown...
August 15, 2016: Oncogene
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