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BAF complex

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https://www.readbyqxmd.com/read/29765770/persistent-6-oh-bde-47-exposure-impairs-functional-neuronal-maturation-and-alters-expression-of-neurodevelopmentally-relevant-chromatin-remodelers
#1
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/29754817/vitamin-d-switches-baf-complexes-to-protect-%C3%AE-cells
#2
Zong Wei, Eiji Yoshihara, Nanhai He, Nasun Hah, Weiwei Fan, Antonio F M Pinto, Timothy Huddy, Yuhao Wang, Brittany Ross, Gabriela Estepa, Yang Dai, Ning Ding, Mara H Sherman, Sungsoon Fang, Xuan Zhao, Christopher Liddle, Annette R Atkins, Ruth T Yu, Michael Downes, Ronald M Evans
A primary cause of disease progression in type 2 diabetes (T2D) is β cell dysfunction due to inflammatory stress and insulin resistance. However, preventing β cell exhaustion under diabetic conditions is a major therapeutic challenge. Here, we identify the vitamin D receptor (VDR) as a key modulator of inflammation and β cell survival. Alternative recognition of an acetylated lysine in VDR by bromodomain proteins BRD7 and BRD9 directs association to PBAF and BAF chromatin remodeling complexes, respectively...
May 7, 2018: Cell
https://www.readbyqxmd.com/read/29728365/a-crispr-knockout-screen-identifies-setdb1-target-retroelement-silencing-factors-in-embryonic-stem-cells
#3
Kei Fukuda, Akihiko Okuda, Kosuke Yusa, Yoichi Shinkai
In mouse embryonic stem cells (mESCs), expression of provirus and endogenous retroelements is epigenetically repressed. Although many cellular factors involved in retroelement silencing have been identified, the complete molecular mechanism remains elusive. In this study, we performed a genome-wide CRISPR screen to advance our understanding of retroelement silencing in mESCs. The Moloney murine leukemia virus (MLV)-based retroviral vector MSCV-GFP, which is repressed by the SETDB1/KAP1 pathway in mESCs was used as a reporter provirus and we identified more than 80 genes involved in this process...
May 4, 2018: Genome Research
https://www.readbyqxmd.com/read/29706634/germline-variants-in-smarcb1-and-other-members-of-the-baf-chromatin-remodeling-complex-across-human-disease-entities-a-meta-analysis
#4
REVIEW
Till Holsten, Susanne Bens, Florian Oyen, Karolina Nemes, Martin Hasselblatt, Uwe Kordes, Reiner Siebert, Michael C Frühwald, Reinhard Schneppenheim, Ulrich Schüller
Germline variants that affect function are found in seven genes of the BAF chromatin-remodeling complex. They are linked to a broad range of diseases that, according to the gene affected, range from non-syndromic or syndromic neurodevelopmental disorders to low-grade tumors and malignancies. In the current meta-analysis, we evaluate genetic and clinical data from more than 400 families and 577 patients affected by BAF germline alterations. We focus on SMARCB1, including 43 unpublished patients from the EU-RHAB registry and our institution...
April 30, 2018: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29650775/mechanotransduction-via-the-linc-complex-regulates-dna-replication-in-myonuclei
#5
Shuoshuo Wang, Elizabeth Stoops, Unnikannan Cp, Barak Markus, Adriana Reuveny, Elly Ordan, Talila Volk
Nuclear mechanotransduction has been implicated in the control of chromatin organization; however, its impact on functional contractile myofibers is unclear. We found that deleting components of the linker of nucleoskeleton and cytoskeleton (LINC) complex in Drosophila melanogaster larval muscles abolishes the controlled and synchronized DNA endoreplication, typical of nuclei across myofibers, resulting in increased and variable DNA content in myonuclei of individual myofibers. Moreover, perturbation of LINC-independent mechanical input after knockdown of β-Integrin in larval muscles similarly led to increased DNA content in myonuclei...
April 12, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29567837/the-brd3-et-domain-recognizes-a-short-peptide-motif-through-a-mechanism-that-is-conserved-across-chromatin-remodelers-and-transcriptional-regulators
#6
Dorothy C Wai, Taylor N Szyszka, Amy E Campbell, Cherry Kwong, Lorna E Wilkinson-White, Ana P G Silva, Jason K K Low, Ann H Kwan, Roland Gamsjaeger, James N Chalmers, Wayne M Patrick, Bin Lu, Christopher R Vakoc, Gerd A Blobel, Joel P Mackay
Members of the bromodomain and extra-terminal domain (BET) family of proteins (bromodomain-containing (BRD) 2, 3, 4 and T) are widely expressed and highly conserved regulators of gene expression in eukaryotes. These proteins have been intimately linked to human disease and more than a dozen clinical trials are currently underway to test BET-protein inhibitors as modulators of cancer therapies. However, although it is clear that these proteins use their bromodomains to bind both histones and transcription factors bearing acetylated lysine residues, the molecular mechanisms by which BET-family proteins regulate gene expression are not well defined...
March 22, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29544705/gene-expression-profiling-of-low-grade-endometrial-stromal-sarcoma-indicates-fusion-protein-mediated-activation-of-the-wnt-signaling-pathway
#7
Joanna Przybyl, Lukasz Kidzinski, Trevor Hastie, Maria Debiec-Rychter, Roel Nusse, Matt van de Rijn
OBJECTIVE: Low-grade endometrial stromal sarcomas (LGESS) harbor chromosomal translocations that affect proteins associated with chromatin remodeling Polycomb Repressive Complex 2 (PRC2), including SUZ12, PHF1 and EPC1. Roughly half of LGESS also demonstrate nuclear accumulation of β-catenin, which is a hallmark of Wnt signaling activation. However, the targets affected by the fusion proteins and the role of Wnt signaling in the pathogenesis of these tumors remain largely unknown. METHODS: Here we report the results of a meta-analysis of three independent gene expression profiling studies on LGESS and immunohistochemical evaluation of nuclear expression of β-catenin and Lef1 in 112 uterine sarcoma specimens obtained from 20 LGESS and 89 LMS patients...
March 12, 2018: Gynecologic Oncology
https://www.readbyqxmd.com/read/29503092/yy1-positively-regulates-transcription-by-targeting-promoters-and-super-enhancers-through-the-baf-complex-in-embryonic-stem-cells
#8
Jia Wang, Xingui Wu, Chao Wei, Xin Huang, Qian Ma, Xiaona Huang, Francesco Faiola, Diana Guallar, Miguel Fidalgo, Tingyuan Huang, Di Peng, Li Chen, Haopeng Yu, Xingyu Li, Junyi Sun, Xinyi Liu, Xiaoxia Cai, Xiao Chen, Ling Wang, Jian Ren, Jianlong Wang, Junjun Ding
Yin Yang 1 (YY1) regulates early embryogenesis and adult tissue formation. However, the role of YY1 in stem cell regulation remains unclear. YY1 has a Polycomb group (PcG) protein-dependent role in mammalian cells. The PcG-independent functions of YY1 are also reported, although their underlying mechanism is still undefined. This paper reports the role of YY1 and BAF complex in the OCT4-mediated pluripotency network in mouse embryonic stem cells (mESCs). The interaction between YY1 and BAF complex promotes mESC proliferation and pluripotency...
April 10, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29482581/the-chromatin-remodeling-subunit-baf200-promotes-normal-hematopoiesis-and-inhibits-leukemogenesis
#9
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/29429572/mutations-in-the-baf-complex-subunit-dpf2-are-associated-with-coffin-siris-syndrome
#10
Georgia Vasileiou, Silvia Vergarajauregui, Sabine Endele, Bernt Popp, Christian Büttner, Arif B Ekici, Marion Gerard, Nuria C Bramswig, Beate Albrecht, Jill Clayton-Smith, Jenny Morton, Susan Tomkins, Karen Low, Astrid Weber, Maren Wenzel, Janine Altmüller, Yun Li, Bernd Wollnik, George Hoganson, Maria-Renée Plona, Megan T Cho, Christian T Thiel, Hermann-Josef Lüdecke, Tim M Strom, Eduardo Calpena, Andrew O M Wilkie, Dagmar Wieczorek, Felix B Engel, André Reis
Variants affecting the function of different subunits of the BAF chromatin-remodelling complex lead to various neurodevelopmental syndromes, including Coffin-Siris syndrome. Furthermore, variants in proteins containing PHD fingers, motifs recognizing specific histone tail modifications, have been associated with several neurological and developmental-delay disorders. Here, we report eight heterozygous de novo variants (one frameshift, two splice site, and five missense) in the gene encoding the BAF complex subunit double plant homeodomain finger 2 (DPF2)...
March 1, 2018: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29391557/smarca2-regulated-host-cell-factors-are-required-for-mxa-restriction-of-influenza-a-viruses
#11
Dominik Dornfeld, Alexandra H Dudek, Thibaut Vausselin, Sira C Günther, Judd F Hultquist, Sebastian Giese, Daria Khokhlova-Cubberley, Yap C Chew, Nevan J Krogan, Adolfo Garcia-Sastre, Martin Schwemmle, Megan L Shaw
The human interferon (IFN)-induced MxA protein is a key antiviral host restriction factor exhibiting broad antiviral activity against many RNA viruses, including highly pathogenic avian influenza A viruses (IAV) of the H5N1 and H7N7 subtype. To date the mechanism for how MxA exerts its antiviral activity is unclear, however, additional cellular factors are believed to be essential for this activity. To identify MxA cofactors we performed a genome-wide siRNA-based screen in human airway epithelial cells (A549) constitutively expressing MxA using an H5N1 reporter virus...
February 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29374542/baffling-pathologies-alterations-of-baf-complexes-in-cancer
#12
Ophelie Arnaud, François Le Loarer, Franck Tirode
To activate or repress specific genes, chromatin is constantly modified by chromatin-remodeling complexes. Among these complexes, the SWItch/Sucrose Non-Fermenting (SWI/SNF) complex, also referred to as BRG1-Associated Factor (BAF) complex, moves the nucleosome along chromatin using energy provided by ATP hydrolysis. In mammalian organisms, the SWI/SNF complex is composed of 10-15 subunits, depending on cell type, and a defect in one of these subunits can have dramatic consequences. In this review we will focus on the alterations identified in the SWI/SNF (BAF) complex subunits that lead to cancerous pathologies...
April 10, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29374058/glioma-tumor-suppressor-candidate-region-gene-1-gltscr1-and-its-paralog-gltscr1-like-form-swi-snf-chromatin-remodeling-subcomplexes
#13
Aktan Alpsoy, Emily C Dykhuizen
The mammalian SWI/SNF chromatin remodeling complex is a heterogeneous collection of related protein complexes required for gene regulation and genome integrity. It contains a central ATPase (BRM or BRG1) and various combinations of 10-14 accessory subunits (BAFs for <u>B</u>RM/BRG1 <u>A</u>ssociated <u>F</u>actor<u>s</u>). Two distinct complexes differing in size, BAF and the slightly larger polybromo-BAF (PBAF), share many of the same core subunits but are differentiated primarily by having either AT-rich interaction domain 1A/B (ARID1A/B in BAF) or ARID2 (in PBAF)...
March 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29360170/a-mendelian-form-of-neural-tube-defect-caused-by-a-de-novo-null-variant-in-smarcc1-in-an-identical-twin
#14
Fuad Al Mutairi, Fatema Alzahrani, Farouq Ababneh, Amna A Kashgari, Fowzan S Alkuraya
Neural tube defects (NTDs) are among the most common birth defects in humans and yet their molecular etiology remains poorly understood. NTDs are believed to result from the complex interaction of environmental factors with a multitude of genetic risk factors in a classical multifactorial disease model. Mendelian forms of NTDs in which single variants are sufficient to cause the disease are extremely rare. We report a monozygotic twin with severe NTDs (occipital encephalocele and myelomeningocele) and a shared de novo, likely truncating, variant in SMARCC1...
February 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29359803/disruption-of-mammalian-swi-snf-and-polycomb-complexes-in-human-sarcomas-mechanisms-and-therapeutic-opportunities
#15
REVIEW
Matthew J McBride, Cigall Kadoch
Soft-tissue sarcomas are increasingly characterized and subclassified by genetic abnormalities that represent underlying drivers of their pathology. Hallmark tumor suppressor gene mutations and pathognomonic gene fusions collectively account for approximately one-third of all sarcomas. These genetic abnormalities most often result in global transcriptional misregulation via disruption of protein regulatory complexes which govern chromatin architecture. Specifically, alterations to mammalian SWI/SNF (mSWI/SNF or BAF) ATP-dependent chromatin remodeling complexes and polycomb repressive complexes cause disease-specific changes in chromatin architecture and gene expression across a number of sarcoma subtypes...
April 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29323272/dominant-negative-smarca4-mutants-alter-the-accessibility-landscape-of-tissue-unrestricted-enhancers
#16
H Courtney Hodges, Benjamin Z Stanton, Katerina Cermakova, Chiung-Ying Chang, Erik L Miller, Jacob G Kirkland, Wai Lim Ku, Vaclav Veverka, Keji Zhao, Gerald R Crabtree
Mutation of SMARCA4 (BRG1), the ATPase of BAF (mSWI/SNF) and PBAF complexes, contributes to a range of malignancies and neurologic disorders. Unfortunately, the effects of SMARCA4 missense mutations have remained uncertain. Here we show that SMARCA4 cancer missense mutations target conserved ATPase surfaces and disrupt the mechanochemical cycle of remodeling. We find that heterozygous expression of mutants alters the open chromatin landscape at thousands of sites across the genome. Loss of DNA accessibility does not directly overlap with Polycomb accumulation, but is enriched in 'A compartments' at active enhancers, which lose H3K27ac but not H3K4me1...
January 2018: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/29281090/novel-reagents-for-human-prolactin-research-large-scale-preparation-and-characterization-of-prolactin-receptor-extracellular-domain-non-pegylated-and-pegylated-prolactin-and-prolactin-receptor-antagonist
#17
Ewa Oclon, Gili Solomon, Zvi Hayouka, Tomer Meir Salame, Vincent Goffin, Arieh Gertler
To provide new tools for in vitro and in vivo prolactin (PRL) research, novel protocols for large-scale preparation of untagged human PRL (hPRL), a hPRL antagonist (del 1-9-G129R hPRL) that acts as a pure antagonist of hPRL in binding to hPRL receptor extracellular domain (hPRLR-ECD), and hPRLR-ECD are demonstrated. The interaction of del 1-9-G129R hPRL with hPRLR-ECD was demonstrated by competitive non-radioactive binding assay using biotinylated hPRL as the ligand and hPRLR-ECD as the receptor, by formation of stable 1:1 complexes with hPRLR-ECD under non-denaturing conditions using size-exclusion chromatography, and by surface plasmon resonance methodology...
January 1, 2018: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/29183906/cardiac-enriched-baf-chromatin-remodeling-complex-subunit-baf60c-regulates-gene-expression-programs-essential-for-heart-development-and-function
#18
Xin Sun, Swetansu K Hota, Yu-Qing Zhou, Stefanie Novak, Dario Miguel-Perez, Danos Christodoulou, Christine E Seidman, J G Seidman, Carol C Gregorio, R Mark Henkelman, Janet Rossant, Benoit G Bruneau
How chromatin-remodeling complexes modulate gene networks to control organ-specific properties is not well understood. For example, Baf60c ( Smarcd3 ) encodes a cardiac-enriched subunit of the SWI/SNF-like BAF chromatin complex, but its role in heart development is not fully understood. We found that constitutive loss of Baf60c leads to embryonic cardiac hypoplasia and pronounced cardiac dysfunction. Conditional deletion of Baf60c in cardiomyocytes resulted in postnatal dilated cardiomyopathy with impaired contractile function...
January 5, 2018: Biology Open
https://www.readbyqxmd.com/read/29136498/a-two-faced-mswi-snf-subunit-dual-roles-for-arid1a-in-tumor-suppression-and-oncogenicity-in-the-liver
#19
Jordan E Otto, Cigall Kadoch
In this issue of Cancer Cell, Sun et al. describe context-dependent oncogenic and tumor-suppressive functions for the mammalian SWI/SNF (BAF) complex subunit ARID1A in the development and progression of hepatocellular carcinoma (HCC).
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29101221/%C3%AE-actin-dependent-global-chromatin-organization-and-gene-expression-programs-control-cellular-identity
#20
Xin Xie, Bader Almuzzaini, Nizar Drou, Stephan Kremb, Ayman Yousif, Ann-Kristin Östlund Farrants, Kristin Gunsalus, Piergiorgio Percipalle
During differentiation and development, cell fate and identity are established by waves of genetic reprogramming. Although the mechanisms are largely unknown, during these events, dynamic chromatin reorganization is likely to ensure that multiple genes involved in the same cellular functions are coregulated, depending on the nuclear environment. In this study, using high-content screening of embryonic fibroblasts from a β-actin knockout (KO) mouse, we found major chromatin rearrangements and changes in histone modifications, such as methylated histone (H)3-lysine-(K)9...
March 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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