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https://www.readbyqxmd.com/read/27762073/cognitive-analysis-of-schizophrenia-risk-genes-that-function-as-epigenetic-regulators-of-gene-expression
#1
Laura Whitton, Donna Cosgrove, Christopher Clarkson, Denise Harold, Kimberley Kendall, Alex Richards, Kiran Mantripragada, Michael J Owen, Michael C O'Donovan, James Walters, Annette Hartmann, Betina Konte, Dan Rujescu, Michael Gill, Aiden Corvin, Stephen Rea, Gary Donohoe, Derek W Morris
Epigenetic mechanisms are an important heritable and dynamic means of regulating various genomic functions, including gene expression, to orchestrate brain development, adult neurogenesis, and synaptic plasticity. These processes when perturbed are thought to contribute to schizophrenia pathophysiology. A core feature of schizophrenia is cognitive dysfunction. For genetic disorders where cognitive impairment is more severe such as intellectual disability, there are a disproportionally high number of genes involved in the epigenetic regulation of gene transcription...
December 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
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
#2
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/27432226/genome-wide-meta-analyses-of-breast-ovarian-and-prostate-cancer-association-studies-identify-multiple-new-susceptibility-loci-shared-by-at-least-two-cancer-types
#3
Siddhartha P Kar, Jonathan Beesley, Ali Amin Al Olama, Kyriaki Michailidou, Jonathan Tyrer, ZSofia Kote-Jarai, Kate Lawrenson, Sara Lindstrom, Susan J Ramus, Deborah J Thompson, Adam S Kibel, Agnieszka Dansonka-Mieszkowska, Agnieszka Michael, Aida K Dieffenbach, Aleksandra Gentry-Maharaj, Alice S Whittemore, Alicja Wolk, Alvaro Monteiro, Ana Peixoto, Andrzej Kierzek, Angela Cox, Anja Rudolph, Anna Gonzalez-Neira, Anna H Wu, Annika Lindblom, Anthony Swerdlow, Argyrios Ziogas, Arif B Ekici, Barbara Burwinkel, Beth Y Karlan, Børge G Nordestgaard, Carl Blomqvist, Catherine Phelan, Catriona McLean, Celeste Leigh Pearce, Celine Vachon, Cezary Cybulski, Chavdar Slavov, Christa Stegmaier, Christiane Maier, Christine B Ambrosone, Claus K Høgdall, Craig C Teerlink, Daehee Kang, Daniel C Tessier, Daniel J Schaid, Daniel O Stram, Daniel W Cramer, David E Neal, Diana Eccles, Dieter Flesch-Janys, Digna R Velez Edwards, Dominika Wokozorczyk, Douglas A Levine, Drakoulis Yannoukakos, Elinor J Sawyer, Elisa V Bandera, Elizabeth M Poole, Ellen L Goode, Elza Khusnutdinova, Estrid Høgdall, Fengju Song, Fiona Bruinsma, Florian Heitz, Francesmary Modugno, Freddie C Hamdy, Fredrik Wiklund, Graham G Giles, Håkan Olsson, Hans Wildiers, Hans-Ulrich Ulmer, Hardev Pandha, Harvey A Risch, Hatef Darabi, Helga B Salvesen, Heli Nevanlinna, Henrik Gronberg, Hermann Brenner, Hiltrud Brauch, Hoda Anton-Culver, Honglin Song, Hui-Yi Lim, Iain McNeish, Ian Campbell, Ignace Vergote, Jacek Gronwald, Jan Lubiński, Janet L Stanford, Javier Benítez, Jennifer A Doherty, Jennifer B Permuth, Jenny Chang-Claude, Jenny L Donovan, Joe Dennis, Joellen M Schildkraut, Johanna Schleutker, John L Hopper, Jolanta Kupryjanczyk, Jong Y Park, Jonine Figueroa, Judith A Clements, Julia A Knight, Julian Peto, Julie M Cunningham, Julio Pow-Sang, Jyotsna Batra, Kamila Czene, Karen H Lu, Kathleen Herkommer, Kay-Tee Khaw, Keitaro Matsuo, Kenneth Muir, Kenneth Offitt, Kexin Chen, Kirsten B Moysich, Kristiina Aittomäki, Kunle Odunsi, Lambertus A Kiemeney, Leon F A G Massuger, Liesel M Fitzgerald, Linda S Cook, Lisa Cannon-Albright, Maartje J Hooning, Malcolm C Pike, Manjeet K Bolla, Manuel Luedeke, Manuel R Teixeira, Marc T Goodman, Marjanka K Schmidt, Marjorie Riggan, Markus Aly, Mary Anne Rossing, Matthias W Beckmann, Matthieu Moisse, Maureen Sanderson, Melissa C Southey, Michael Jones, Michael Lush, Michelle A T Hildebrandt, Ming-Feng Hou, Minouk J Schoemaker, Montserrat Garcia-Closas, Natalia Bogdanova, Nazneen Rahman, Nhu D Le, Nick Orr, Nicolas Wentzensen, Nora Pashayan, Paolo Peterlongo, Pascal Guénel, Paul Brennan, Paula Paulo, Penelope M Webb, Per Broberg, Peter A Fasching, Peter Devilee, Qin Wang, Qiuyin Cai, Qiyuan Li, Radka Kaneva, Ralf Butzow, Reidun Kristin Kopperud, Rita K Schmutzler, Robert A Stephenson, Robert J MacInnis, Robert N Hoover, Robert Winqvist, Roberta Ness, Roger L Milne, Ruth C Travis, Sara Benlloch, Sara H Olson, Shannon K McDonnell, Shelley S Tworoger, Sofia Maia, Sonja Berndt, Soo Chin Lee, Soo-Hwang Teo, Stephen N Thibodeau, Stig E Bojesen, Susan M Gapstur, Susanne Krüger Kjær, Tanja Pejovic, Teuvo L J Tammela, Thilo Dörk, Thomas Brüning, Tiina Wahlfors, Tim J Key, Todd L Edwards, Usha Menon, Ute Hamann, Vanio Mitev, Veli-Matti Kosma, Veronica Wendy Setiawan, Vessela Kristensen, Volker Arndt, Walther Vogel, Wei Zheng, Weiva Sieh, William J Blot, Wojciech Kluzniak, Xiao-Ou Shu, Yu-Tang Gao, Fredrick Schumacher, Matthew L Freedman, Andrew Berchuck, Alison M Dunning, Jacques Simard, Christopher A Haiman, Amanda Spurdle, Thomas A Sellers, David J Hunter, Brian E Henderson, Peter Kraft, Stephen J Chanock, Fergus J Couch, Per Hall, Simon A Gayther, Douglas F Easton, Georgia Chenevix-Trench, Rosalind Eeles, Paul D P Pharoah, Diether Lambrechts
UNLABELLED: Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10(-8) seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3)...
September 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27031336/isolation-of-a-genomic-region-affecting-most-components-of-metabolic-syndrome-in-a-chromosome-16-congenic-rat-model
#4
Lucie Šedová, Michal Pravenec, Drahomíra Křenová, Ludmila Kazdová, Václav Zídek, Michaela Krupková, František Liška, Vladimír Křen, Ondřej Šeda
Metabolic syndrome is a highly prevalent human disease with substantial genomic and environmental components. Previous studies indicate the presence of significant genetic determinants of several features of metabolic syndrome on rat chromosome 16 (RNO16) and the syntenic regions of human genome. We derived the SHR.BN16 congenic strain by introgression of a limited RNO16 region from the Brown Norway congenic strain (BN-Lx) into the genomic background of the spontaneously hypertensive rat (SHR) strain. We compared the morphometric, metabolic, and hemodynamic profiles of adult male SHR and SHR...
2016: PloS One
https://www.readbyqxmd.com/read/25825869/the-tumour-suppressor-chd5-forms-a-nurd-type-chromatin-remodelling-complex
#5
Venkatadri Kolla, Koumudi Naraparaju, Tiangang Zhuang, Mayumi Higashi, Sriharsha Kolla, Gerd A Blobel, Garrett M Brodeur
Eukaryotic gene expression is developmentally regulated, in part by chromatin remodelling, and its dysregulation has been linked to cancer. CHD5 (chromodomain helicase DNA-binding protein 5) is a tumour suppressor gene (TSG) that maps to a region of consistent deletion on 1p36.31 in neuroblastomas (NBs) and other tumour types. CHD5 encodes a protein with chromatin remodelling, helicase and DNA-binding motifs that is preferentially expressed in neural and testicular tissues. CHD5 is highly homologous to CHD3 and CHD4, which are the core subunits of nucleosome remodelling and deacetylation (NuRD) complexes...
June 1, 2015: Biochemical Journal
https://www.readbyqxmd.com/read/25796366/structure-and-function-insights-into-the-nurd-chromatin-remodeling-complex
#6
REVIEW
Morgan P Torchy, Ali Hamiche, Bruno P Klaholz
Transcription regulation through chromatin compaction and decompaction is regulated through various chromatin-remodeling complexes such as nucleosome remodeling and histone deacetylation (NuRD) complex. NuRD is a 1 MDa multi-subunit protein complex which comprises many different subunits, among which histone deacetylases HDAC1/2, ATP-dependent remodeling enzymes CHD3/4, histone chaperones RbAp46/48, CpG-binding proteins MBD2/3, the GATAD2a (p66α) and/or GATAD2b (p66β) and specific DNA-binding proteins MTA1/2/3...
July 2015: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/23239876/unique-features-of-the-anti-parallel-heterodimeric-coiled-coil-interaction-between-methyl-cytosine-binding-domain-2-mbd2-homologues-and-gata-zinc-finger-domain-containing-2a-gatad2a-p66%C3%AE
#7
Ninad M Walavalkar, Nathaniel Gordon, David C Williams
The methyl-cytosine binding domain 2 (MBD2)-nucleosome remodeling and deacetylase (NuRD) complex recognizes methylated DNA and silences expression of associated genes through histone deacetylase and nucleosome remodeling functions. Our previous structural work demonstrated that a coiled-coil interaction between MBD2 and GATA zinc finger domain containing 2A (GATAD2A/p66α) proteins recruits the chromodomain helicase DNA-binding protein (CHD4/Mi2β) to the NuRD complex and is necessary for MBD2-mediated DNA methylation-dependent gene silencing in vivo (Gnanapragasam, M...
February 1, 2013: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/22325160/large-scale-gene-centric-meta-analysis-across-39-studies-identifies-type-2-diabetes-loci
#8
Richa Saxena, Clara C Elbers, Yiran Guo, Inga Peter, Tom R Gaunt, Jessica L Mega, Matthew B Lanktree, Archana Tare, Berta Almoguera Castillo, Yun R Li, Toby Johnson, Marcel Bruinenberg, Diane Gilbert-Diamond, Ramakrishnan Rajagopalan, Benjamin F Voight, Ashok Balasubramanyam, John Barnard, Florianne Bauer, Jens Baumert, Tushar Bhangale, Bernhard O Böhm, Peter S Braund, Paul R Burton, Hareesh R Chandrupatla, Robert Clarke, Rhonda M Cooper-DeHoff, Errol D Crook, George Davey-Smith, Ian N Day, Anthonius de Boer, Mark C H de Groot, Fotios Drenos, Jane Ferguson, Caroline S Fox, Clement E Furlong, Quince Gibson, Christian Gieger, Lisa A Gilhuijs-Pederson, Joseph T Glessner, Anuj Goel, Yan Gong, Struan F A Grant, Diederick E Grobbee, Claire Hastie, Steve E Humphries, Cecilia E Kim, Mika Kivimaki, Marcus Kleber, Christa Meisinger, Meena Kumari, Taimour Y Langaee, Debbie A Lawlor, Mingyao Li, Maximilian T Lobmeyer, Anke-Hilse Maitland-van der Zee, Matthijs F L Meijs, Cliona M Molony, David A Morrow, Gurunathan Murugesan, Solomon K Musani, Christopher P Nelson, Stephen J Newhouse, Jeffery R O'Connell, Sandosh Padmanabhan, Jutta Palmen, Sanjey R Patel, Carl J Pepine, Mary Pettinger, Thomas S Price, Suzanne Rafelt, Jane Ranchalis, Asif Rasheed, Elisabeth Rosenthal, Ingo Ruczinski, Sonia Shah, Haiqing Shen, Günther Silbernagel, Erin N Smith, Annemieke W M Spijkerman, Alice Stanton, Michael W Steffes, Barbara Thorand, Mieke Trip, Pim van der Harst, Daphne L van der A, Erik P A van Iperen, Jessica van Setten, Jana V van Vliet-Ostaptchouk, Niek Verweij, Bruce H R Wolffenbuttel, Taylor Young, M Hadi Zafarmand, Joseph M Zmuda, Michael Boehnke, David Altshuler, Mark McCarthy, W H Linda Kao, James S Pankow, Thomas P Cappola, Peter Sever, Neil Poulter, Mark Caulfield, Anna Dominiczak, Denis C Shields, Deepak L Bhatt, Deepak Bhatt, Li Zhang, Sean P Curtis, John Danesh, Juan P Casas, Yvonne T van der Schouw, N Charlotte Onland-Moret, Pieter A Doevendans, Gerald W Dorn, Martin Farrall, Garret A FitzGerald, Anders Hamsten, Robert Hegele, Aroon D Hingorani, Marten H Hofker, Gordon S Huggins, Thomas Illig, Gail P Jarvik, Julie A Johnson, Olaf H Klungel, William C Knowler, Wolfgang Koenig, Winfried März, James B Meigs, Olle Melander, Patricia B Munroe, Braxton D Mitchell, Susan J Bielinski, Daniel J Rader, Muredach P Reilly, Stephen S Rich, Jerome I Rotter, Danish Saleheen, Nilesh J Samani, Eric E Schadt, Alan R Shuldiner, Roy Silverstein, Kandice Kottke-Marchant, Philippa J Talmud, Hugh Watkins, Folkert W Asselbergs, Folkert Asselbergs, Paul I W de Bakker, Jeanne McCaffery, Cisca Wijmenga, Marc S Sabatine, James G Wilson, Alex Reiner, Donald W Bowden, Hakon Hakonarson, David S Siscovick, Brendan J Keating
To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom ∼50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with ∼2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis of 25 studies comprising 14,073 cases and 57,489 controls of European descent confirmed eight established T2D loci at genome-wide significance. In silico follow-up analysis of putative association signals found in independent genome-wide association studies (including 8,130 cases and 38,987 controls) performed by the DIAGRAM consortium identified a T2D locus at genome-wide significance (GATAD2A/CILP2/PBX4; p = 5...
March 9, 2012: American Journal of Human Genetics
https://www.readbyqxmd.com/read/17565372/mutants-in-the-mouse-nurd-mi2-component-p66alpha-are-embryonic-lethal
#9
Susan Marino, Roel Nusse
BACKGROUND: The NuRD/Mi2 chromatin complex is involved in histone modifications and contains a large number of subunits, including the p66 protein. There are two mouse and human p66 paralogs, p66alpha and p66beta. The functions of these genes are not clear, in part because there are no mutants available, except in invertebrate model systems. METHODOLOGY: We made loss of function mutants in the mouse p66alpha gene (mp66alpha, official name Gatad2a, MGI:2384585). We found that mp66alpha is essential for development, as mutant embryos die around day 10 of embryogenesis...
2007: PloS One
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