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BAF complex

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https://www.readbyqxmd.com/read/28717667/haploinsufficiency-of-bcl11a-associated-with-cerebellar-abnormalities-in-2p15p16-1-deletion-syndrome
#1
Hiroko Shimbo, Takayuki Yokoi, Noriko Aida, Seiji Mizuno, Hiroshi Suzumura, Junichi Nagai, Kazumi Ida, Yumi Enomoto, Chihiro Hatano, Kenji Kurosawa
BACKGROUND: Chromosome 2p15p16.1 deletion syndrome is a rare genetic disorder characterized by intellectual disability (ID), neurodevelopmental delay, language delay, growth retardation, microcephaly, structural brain abnormalities, and dysmorphic features. More than 30 patients with 2p15p16.1 microdeletion syndrome have been reported in the literature. METHODS: Molecular analysis was performed using microarray-based comparative genomic hybridization (array CGH)...
July 2017: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/28706277/dna-binding-drives-the-association-of-brg1-hbrm-bromodomains-with-nucleosomes
#2
Emma A Morrison, Julio C Sanchez, Jehnna L Ronan, Daniel P Farrell, Katayoun Varzavand, Jenna K Johnson, Brian X Gu, Gerald R Crabtree, Catherine A Musselman
BRG1 and BRM, central components of the BAF (mSWI/SNF) chromatin remodelling complex, are critical in chromatin structure regulation. Here, we show that the human BRM (hBRM) bromodomain (BRD) has moderate specificity for H3K14ac. Surprisingly, we also find that both BRG1 and hBRM BRDs have DNA-binding activity. We demonstrate that the BRDs associate with DNA through a surface basic patch and that the BRD and an adjacent AT-hook make multivalent contacts with DNA, leading to robust affinity and moderate specificity for AT-rich elements...
July 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28692054/modeling-cancer-driver-events-in-vitro-using-barrier-bypass-clonal-expansion-assays-and-massively-parallel-sequencing
#3
H Huskova, M Ardin, A Weninger, K Vargova, S Barrin, S Villar, M Olivier, T Stopka, Z Herceg, M Hollstein, J Zavadil, M Korenjak
The information on candidate cancer driver alterations available from public databases is often descriptive and of limited mechanistic insight, which poses difficulties for reliable distinction between true driver and passenger events. To address this challenge, we performed in-depth analysis of whole-exome sequencing data from cell lines generated by a barrier bypass-clonal expansion (BBCE) protocol. The employed strategy is based on carcinogen-driven immortalization of primary mouse embryonic fibroblasts and recapitulates early steps of cell transformation...
July 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28688381/zeroth-order-regular-approximation-approach-to-electric-dipole-moment-interactions-of-the-electron
#4
Konstantin Gaul, Robert Berger
A quasi-relativistic two-component approach for an efficient calculation of P,T-odd interactions caused by a permanent electric dipole moment of the electron (eEDM) is presented. The approach uses a (two-component) complex generalized Hartree-Fock and a complex generalized Kohn-Sham scheme within the zeroth order regular approximation. In applications to select heavy-elemental polar diatomic molecular radicals, which are promising candidates for an eEDM experiment, the method is compared to relativistic four-component electron-correlation calculations and confirms values for the effective electric field acting on the unpaired electron for RaF, BaF, YbF, and HgF...
July 7, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28649782/heterozygous-variants-in-actl6a-encoding-a-component-of-the-baf-complex-are-associated-with-intellectual-disability
#5
Ronit Marom, Mahim Jain, Lindsay C Burrage, I-Wen Song, Brett H Graham, Chester W Brown, Servi J C Stevens, Alexander P A Stegmann, Andrew T Gunter, Julie D Kaplan, Ralitza H Gavrilova, Marwan Shinawi, Jill A Rosenfeld, Yangjin Bae, Alyssa A Tran, Yuqing Chen, James T Lu, Richard A Gibbs, Christine Eng, Yaping Yang, Justine Rousseau, Bert B A de Vries, Philippe M Campeau, Brendan Lee
Pathogenic variants in genes encoding components of the BRG1-associated factor (BAF) chromatin remodeling complex have been associated with intellectual disability syndromes. We identified heterozygous, novel variants in ACTL6A, a gene encoding a component of the BAF complex, in three subjects with varying degrees of intellectual disability. Two subjects have missense variants affecting highly conserved amino acid residues within the actin-like domain. Missense mutations in the homologous region in yeast actin were previously reported to be dominant lethal and were associated with impaired binding of the human ACTL6A to β-actin and BRG1...
June 25, 2017: Human Mutation
https://www.readbyqxmd.com/read/28611094/agonist-specific-protein-interactomes-of-glucocorticoid-and-androgen-receptor-as-revealed-by-proximity-mapping
#6
Joanna K Lempiäinen, Einari A Niskanen, Kaisa-Mari Vuoti, Riikka E Lampinen, Helka Göös, Markku Varjosalo, Jorma J Palvimo
Glucocorticoid receptor (GR) and androgen receptor (AR) are steroid-inducible transcription factors (TFs). The GR and the AR are central regulators of various metabolic, homeostatic and differentiation processes and hence important therapeutic targets, especially in inflammation and prostate cancer, respectively. Hormone binding to these steroid receptors (SRs) leads to DNA binding and activation or repression of their target genes with the aid of interacting proteins, coregulators. However, protein interactomes of these important drug targets have remained poorly defined...
August 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28446594/pioneering-ebf2-remodels-the-brown-fat-chromatin-landscape
#7
Jiexin Wang, Peter Tontonoz
In this issue of Genes & Development, Shapira and colleagues (pp. 660-673) outline mechanisms by which the brown fat transcription factor early B-cell factor 2 (EBF2) selectively activates brown lineage-specific gene expression. The investigators show that EBF2 interacts with and recruits a tissue-specific BAF chromatin remodeling complex to brown fat gene enhancers, thereby regulating chromatin accessibility. Their findings provide important insight into epigenetic regulation of adipocyte fate and thermogenic gene expression...
April 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28438634/structural-insights-into-baf47-and-baf155-complex-formation
#8
Li Yan, Si Xie, Yongming Du, Chengmin Qian
Mammalian BAF complexes are a subfamily of SWI/SNF ATP-dependent chromatin remodelers that dynamically modulate chromatin structure to regulate fundamental cellular processes including gene transcription, cell cycle control, and DNA damage response. So far, many distinct BAF complexes have been identified with polymorphic assemblies of up to 15 subunits from 29 genes. The evolutionarily conserved BRG1/BRM, BAF47, and BAF155/BAF170 form a stable complex that carries out essential chromatin remodeling activity and therefore have been regarded as the core components of BAF complex...
June 2, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28438527/the-baf-brg1-brm-associated-factor-chromatin-remodeling-complex-exhibits-ethanol-sensitivity-in-fetal-neural-progenitor-cells-and-regulates-transcription-at-the-mir-9-2-encoding-gene-locus
#9
Sasha G Burrowes, Nihal A Salem, Alexander M Tseng, Sridevi Balaraman, Marisa R Pinson, Cadianna Garcia, Rajesh C Miranda
Fetal alcohol spectrum disorders are a leading cause of intellectual disability worldwide. Previous studies have shown that developmental ethanol exposure results in loss of microRNAs (miRNAs), including miR-9, and loss of these miRNAs, in turn, mediates some of ethanol's teratogenic effects in the developing brain. We previously found that ethanol increased methylation at the miR-9-2 encoding gene locus in mouse fetal neural stem cells (NSC), advancing a mechanism for epigenetic silencing of this locus and consequently, miR-9 loss in NSCs...
May 2017: Alcohol
https://www.readbyqxmd.com/read/28428261/ebf2-transcriptionally-regulates-brown-adipogenesis-via-the-histone-reader-dpf3-and-the-baf-chromatin-remodeling-complex
#10
Suzanne N Shapira, Hee-Woong Lim, Sona Rajakumari, Alexander P Sakers, Jeff Ishibashi, Matthew J Harms, Kyoung-Jae Won, Patrick Seale
The transcription factor early B-cell factor 2 (EBF2) is an essential mediator of brown adipocyte commitment and terminal differentiation. However, the mechanisms by which EBF2 regulates chromatin to activate brown fat-specific genes in adipocytes were unknown. ChIP-seq (chromatin immunoprecipitation [ChIP] followed by deep sequencing) analyses in brown adipose tissue showed that EBF2 binds and regulates the activity of lineage-specific enhancers. Mechanistically, EBF2 physically interacts with the chromatin remodeler BRG1 and the BAF chromatin remodeling complex in brown adipocytes...
April 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28418626/degradation-of-the-baf-complex-factor-brd9-by-heterobifunctional-ligands
#11
David Remillard, Dennis L Buckley, Joshiawa Paulk, Gerard L Brien, Matthew Sonnett, Hyuk-Soo Seo, Shiva Dastjerdi, Martin Wühr, Sirano Dhe-Paganon, Scott A Armstrong, James E Bradner
The bromodomain-containing protein BRD9, a subunit of the human BAF (SWI/SNF) nucleosome remodeling complex, has emerged as an attractive therapeutic target in cancer. Despite the development of chemical probes targeting the BRD9 bromodomain, there is a limited understanding of BRD9 function beyond acetyl-lysine recognition. We have therefore created the first BRD9-directed chemical degraders, through iterative design and testing of heterobifunctional ligands that bridge the BRD9 bromodomain and the cereblon E3 ubiquitin ligase complex...
May 15, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28416631/mutation-of-neuron-specific-chromatin-remodeling-subunit-baf53b-rescue-of-plasticity-and-memory-by-manipulating-actin-remodeling
#12
Annie Vogel Ciernia, Enikö A Kramár, Dina P Matheos, Robbert Havekes, Thekla J Hemstedt, Christophe N Magnan, Keith Sakata, Ashley Tran, Soraya Azzawi, Alberto Lopez, Richard Dang, Weisheng Wang, Brian Trieu, Joyce Tong, Ruth M Barrett, Rebecca J Post, Pierre Baldi, Ted Abel, Gary Lynch, Marcelo A Wood
Recent human exome-sequencing studies have implicated polymorphic Brg1-associated factor (BAF) complexes (mammalian SWI/SNF chromatin remodeling complexes) in several intellectual disabilities and cognitive disorders, including autism. However, it remains unclear how mutations in BAF complexes result in impaired cognitive function. Post-mitotic neurons express a neuron-specific assembly, nBAF, characterized by the neuron-specific subunit BAF53b. Subdomain 2 of BAF53b is essential for the differentiation of neuronal precursor cells into neurons...
May 2017: Learning & Memory
https://www.readbyqxmd.com/read/28408647/composition-and-function-of-mammalian-swi-snf-chromatin-remodeling-complexes-in-human-disease
#13
John L Pulice, Cigall Kadoch
Mammalian SWI/SNF (BAF) chromatin remodeling complexes play critical roles in maintaining chromatin architecture and gene expression. Genomic sequencing efforts over the past several years have unveiled a major role for these complexes in the development of human cancer as well as neurologic disease, prompting the need to interrogate underlying mechanisms and to develop new methods to comprehensively understand mSWI/SNF complex function. Here we discuss the emerging insights from genetic, biochemical, and functional genomic studies in the field and suggest approaches toward further basic investigations, as well as therapeutic targeting of chromatin remodeling machinery...
April 13, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28391084/mammalian-swi-snf-complexes-in-cancer-emerging-therapeutic-opportunities
#14
REVIEW
Roodolph St Pierre, Cigall Kadoch
Mammalian SWI/SNF (BAF) chromatin remodeling complexes orchestrate a diverse set of chromatin alterations which impact transcriptional output. Recent whole-exome sequencing efforts have revealed that the genes encoding subunits of mSWI/SNF complexes are mutated in over 20% of cancers, spanning a wide range of tissue types. The majority of mutations result in loss of subunit protein expression, implicating mSWI/SNF subunits as tumor suppressors. mSWI/SNF-deficient cancers remain a therapeutic challenge, owing to a lack of potent and selective agents which target complexes or unique pathway dependencies generated by mSWI/SNF subunit perturbations...
April 6, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28381560/the-chromatin-remodeling-subunit-baf200-promotes-homology-directed-dna-repair-and-regulates-distinct-chromatin-remodeling-complexes
#15
Rodrigo O de Castro, Luciana Previato, Victor Goitea, Anna Felberg, Michel F Guiraldelli, Adrian Filiberti, Roberto J Pezza
The efficiency and type of pathway chosen to repair DNA double-strand breaks (DSBs) are critically influenced by the nucleosome packaging and the chromatin architecture surrounding the DSBs. The Swi/Snf (PBAF and BAF) chromatin-remodeling complexes contribute to DNA damage-induced nucleosome remodeling, but the mechanism by which it contributes to this function is poorly understood. Herein, we report how the Baf200 (Arid2) PBAF-defining subunit regulates DSB repair. We used cytological and biochemical approaches to show that Baf200 plays an important function by facilitating homologous recombination-dependent processes, such as recruitment of Rad51 (a key component of homologous recombination) to DSBs, homology-directed repair, and cell survival after DNA damage...
May 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28369034/smarcd2-subunit-of-swi-snf-chromatin-remodeling-complexes-mediates-granulopoiesis-through-a-cebp%C3%A9-dependent-mechanism
#16
Pierre Priam, Veneta Krasteva, Philippe Rousseau, Giovanni D'Angelo, Louis Gaboury, Guy Sauvageau, Julie A Lessard
Recent studies suggest that individual subunits of chromatin-remodeling complexes produce biologically specific meaning in different cell types through combinatorial assembly. Here we show that granulocyte development requires SMARCD2, a subunit of ATP-dependent SWI/SNF (BAF) chromatin-remodeling complexes. Smarcd2-deficient mice fail to generate functionally mature neutrophils and eosinophils, a phenotype reminiscent of neutrophil-specific granule deficiency (SGD) in humans, for which loss-of-function mutations in CEBPE (encoding CEBPɛ) have been reported...
May 2017: Nature Genetics
https://www.readbyqxmd.com/read/28270570/baf53b-a-neuron-specific-nucleosome-remodeling-factor-is-induced-after-learning-and-facilitates-long-term-memory-consolidation
#17
Miran Yoo, Kwang-Yeon Choi, Jieun Kim, Mujun Kim, Jaehoon Shim, Jun-Hyeok Choi, Hye-Yeon Cho, Jung-Pyo Oh, Hyung-Su Kim, Bong-Kiun Kaang, Jin-Hee Han
Although epigenetic mechanisms of gene expression regulation have recently been implicated in memory consolidation and persistence, the role of nucleosome-remodeling is largely unexplored. Recent studies show that the functional loss of BAF53b, a postmitotic neuron-specific subunit of the BAF nucleosome-remodeling complex, results in the deficit of consolidation of hippocampus-dependent memory and cocaine-associated memory in the rodent brain. However, it is unclear whether BAF53b expression is regulated during memory formation and how BAF53b regulates fear memory in the amygdala, a key brain site for fear memory encoding and storage...
March 29, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28262751/the-swi-snf-chromatin-remodelling-complex-is-required-for-maintenance-of-lineage-specific-enhancers
#18
Burak H Alver, Kimberly H Kim, Ping Lu, Xiaofeng Wang, Haley E Manchester, Weishan Wang, Jeffrey R Haswell, Peter J Park, Charles W M Roberts
Genes encoding subunits of SWI/SNF (BAF) chromatin remodelling complexes are collectively altered in over 20% of human malignancies, but the mechanisms by which these complexes alter chromatin to modulate transcription and cell fate are poorly understood. Utilizing mouse embryonic fibroblast and cancer cell line models, here we show via ChIP-seq and biochemical assays that SWI/SNF complexes are preferentially targeted to distal lineage specific enhancers and interact with p300 to modulate histone H3 lysine 27 acetylation...
March 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28250416/top2-synergizes-with-baf-chromatin-remodeling-for-both-resolution-and-formation-of-facultative-heterochromatin
#19
Erik L Miller, Diana C Hargreaves, Cigall Kadoch, Chiung-Ying Chang, Joseph P Calarco, Courtney Hodges, Jason D Buenrostro, Kairong Cui, William J Greenleaf, Keji Zhao, Gerald R Crabtree
The resolution and formation of facultative heterochromatin are essential for development, reprogramming, and oncogenesis. The mechanisms underlying these changes are poorly understood owing to the difficulty of studying heterochromatin dynamics and structure in vivo. We devised an in vivo approach to investigate these mechanisms and found that topoisomerase II (TOP2), but not TOP1, synergizes with BAF (mSWI/SNF) ATP-dependent chromatin remodeling complexes genome-wide to resolve facultative heterochromatin to accessible chromatin independent of transcription...
April 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28193841/dual-roles-of-akirin2-protein-during-xenopus-neural-development
#20
Xiaoliang Liu, Yingjie Xia, Jixin Tang, Li Ma, Chaocui Li, Pengcheng Ma, Bingyu Mao
To ensure correct spatial and temporal patterning, embryos must maintain pluripotent cell populations and control when cells undergo commitment. The newly identified nucleoprotein Akirin has been shown to modulate the innate immune response through epigenetic regulation and to play important roles in other physiological processes, but its role in neural development remains unknown. Here we show that Akirin2 is required for neural development in Xenopus and that knockdown of Akirin2 expands the expression of the neural progenitor marker Sox2 and inhibits expression of the differentiated neuronal marker N-tubulin...
April 7, 2017: Journal of Biological Chemistry
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