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https://www.readbyqxmd.com/read/29483235/smarcb1-deficiency-integrates-epigenetic-signals-to-oncogenic-gene-expression-program-maintenance-in-human-acute-myeloid-leukemia
#1
Shankha Subhra Chatterjee, Mayukh Biswas, Liberalis Debraj Boila, Debasis Banerjee, Amitava Sengupta
SWI/SNF is an evolutionarily conserved multi-subunit chromatin remodeling complex that regulates epigenetic architecture and cellular identity. Although SWI/SNF genes are altered in ~ 25% of human malignancies, evidences showing their involvement in tumor cell-autonomous chromatin regulation and transcriptional plasticity are limiting. This study demonstrates that human primary acute myeloid leukemia (AML) cells exhibit near complete loss of SMARCB1 (BAF47 or SNF5/INI1) and SMARCD2 (BAF60B) associated with nucleation of SWI/SNFΔ...
February 26, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29434212/carm1-expressing-ovarian-cancer-depends-on-the-histone-methyltransferase-ezh2-activity
#2
Sergey Karakashev, Hengrui Zhu, Shuai Wu, Yuhki Yokoyama, Benjamin G Bitler, Pyoung-Hwa Park, Jeong-Heon Lee, Andrew V Kossenkov, Krutika Satish Gaonkar, Huihuang Yan, Ronny Drapkin, Jose R Conejo-Garcia, David W Speicher, Tamas Ordog, Rugang Zhang
CARM1 is an arginine methyltransferase that asymmetrically dimethylates protein substrates on arginine residues. CARM1 is often overexpressed in human cancers. However, clinically applicable cancer therapeutic strategies based on CARM1 expression remain to be explored. Here, we report that EZH2 inhibition is effective in CARM1-expressing epithelial ovarian cancer. Inhibition of EZH2 activity using a clinically applicable small molecule inhibitor significantly suppresses the growth of CARM1-expressing, but not CARM1-deficient, ovarian tumors in two xenograft models and improves the survival of mice bearing CARM1-expressing ovarian tumors...
February 12, 2018: Nature Communications
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
#3
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 BRM/BRG1 Associated Factors). 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)...
January 26, 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
#4
Fuad Al Mutairi, Fatema Alzahrani, Farouq Ababneh, Amna A Kashgari, Fowzan S Alkuraya
Neural tube defects (NTD) are among the most common birth defects in humans and yet their molecular etiology remains poorly understood. NTD 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 NTD in which single variants are sufficient to cause the disease are extremely rare. We report a monozygotic twin with severe NTD (occipital encephalocele and myelomeningocele) and a shared de novo likely truncating variant in SMARCC1...
January 23, 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29024220/differential-expression-of-key-subunits-of-swi-snf-chromatin-remodeling-complexes-in-porcine-embryos-derived-in-vitro-or-in-vivo
#5
Birgit Cabot, Yu-Chun Tseng, Jennifer S Crodian, Ryan Cabot
In vitro embryo production is an established method for both humans and animals, but is fraught with inferior development and health issues in offspring born after in vitro fertilization procedures. Analysis of epigenetic changes caused by exposure to in vitro conditions should shed light on potential sources of these phenotypes. Using immunocytochemistry, we investigated the localization and relative abundance of components associated with the SWI/SNF (Switch/Sucrose non-fermentable) chromatin-remodeling complex-including BAF155, BAF170, BAF180, BAF53A, BAF57, BAF60A, BAF45D, ARID1A, ARID1B, ARID2, SNF5, and BRD7-in oocytes and in in vitro-produced and in vivo-derived porcine embryos...
December 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/28939766/casein-kinase-2-mediated-phosphorylation-of-brahma-related-gene-1-controls-myoblast-proliferation-and-contributes-to-swi-snf-complex-composition
#6
Teresita Padilla-Benavides, Brian T Nasipak, Amanda L Paskavitz, Dominic T Haokip, Jake M Schnabl, Jeffrey A Nickerson, Anthony N Imbalzano
Transcriptional regulation is modulated in part by chromatin-remodeling enzymes that control gene accessibility by altering chromatin compaction or nucleosome positioning. Brahma-related gene 1 (Brg1), a catalytic subunit of the mammalian SWI/SNF chromatin-remodeling enzymes, is required for both myoblast proliferation and differentiation, and the control of Brg1 phosphorylation by calcineurin, PKCβ1, and p38 regulates the transition to differentiation. However, we hypothesized that Brg1 activity might be regulated by additional kinases...
November 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28717195/stability-of-the-phf10-subunit-of-pbaf-signature-module-is-regulated-by-phosphorylation-role-of-%C3%AE-trcp
#7
Victor V Tatarskiy, Yuriy P Simonov, Dmitrii S Shcherbinin, Alexander V Brechalov, Sofia G Georgieva, Nataliya V Soshnikova
The PBAF chromatin-remodeling complexes are multi-protein machines, regulating expression of genes involved in proliferation and differentiation. PHF10 is a subunit of the PBAF essential for its association with chromatin. Mammalian PHF10 is expressed as four ubiquitous isoforms, which are alternatively incorporated in the complex and differ by their influence on transcription of target genes. PHF10 have different domain structure and two of them (PHF10-S isoforms) lack C-terminal PHD domains, which enables their phosphorylation by CK-1...
July 17, 2017: Scientific Reports
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/27914010/recruitment-by-the-repressor-freud-1-of-histone-deacetylase-brg1-chromatin-remodeling-complexes-to-strengthen-htr1a-gene-repression
#10
Tatiana Souslova, Kim Mirédin, Anne M Millar, Paul R Albert
Five-prime repressor element under dual repression binding protein-1 (Freud-1)/CC2D1A is genetically linked to intellectual disability and implicated in neuronal development. Freud-1 represses the serotonin-1A (5-HT1A) receptor gene HTR1A by histone deacetylase (HDAC)-dependent or HDAC-independent mechanisms in 5-HT1A-negative (e.g., HEK-293) or 5-HT1A-expressing cells (SK-N-SH), respectively. To identify the underlying mechanisms, Freud-1-associated proteins were affinity-purified from HEK-293 nuclear extracts and members of the Brg1/SMARCCA chromatin remodeling and Sin3A-HDAC corepressor complexes were identified...
December 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/27611684/mswi-snf-baf-complexes-are-indispensable-for-the-neurogenesis-and-development-of-embryonic-olfactory-epithelium
#11
Christina Bachmann, Huong Nguyen, Joachim Rosenbusch, Linh Pham, Tamara Rabe, Megha Patwa, Godwin Sokpor, Rho H Seong, Ruth Ashery-Padan, Ahmed Mansouri, Anastassia Stoykova, Jochen F Staiger, Tran Tuoc
Neurogenesis is a key developmental event through which neurons are generated from neural stem/progenitor cells. Chromatin remodeling BAF (mSWI/SNF) complexes have been reported to play essential roles in the neurogenesis of the central nervous system. However, whether BAF complexes are required for neuron generation in the olfactory system is unknown. Here, we identified onscBAF and ornBAF complexes, which are specifically present in olfactory neural stem cells (oNSCs) and olfactory receptor neurons (ORNs), respectively...
September 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27479032/carm1-methylates-chromatin-remodeling-factor-baf155-to-enhance-tumor-progression-and-metastasis
#12
Lu Wang, Zibo Zhao, Mark B Meyer, Sandeep Saha, Menggang Yu, Ailan Guo, Kari B Wisinski, Wei Huang, Weibo Cai, J Wesley Pike, Ming Yuan, Paul Ahlquist, Wei Xu
No abstract text is available yet for this article.
July 11, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27378238/identification-of-epigenetic-factor-proteins-expressed-in-human-embryonic-stem-cell-derived-trophoblasts-and-in-human-placental-trophoblasts
#13
Prasenjit Sarkar, Adam Mischler, Shan M Randall, Timothy S Collier, Karen F Dorman, Kim A Boggess, David C Muddiman, Balaji M Rao
Human embryonic stem cells (hESCs) have been used to derive trophoblasts through differentiation in vitro. Intriguingly, mouse ESCs are prevented from differentiation to trophoblasts by certain epigenetic factor proteins such as Dnmt1, thus necessitating the study of epigenetic factor proteins during hESC differentiation to trophoblasts. We used stable isotope labeling by amino acids in cell culture and quantitative proteomics to study changes in the nuclear proteome during hESC differentiation to trophoblasts and identified changes in the expression of 30 epigenetic factor proteins...
August 5, 2016: Journal of Proteome Research
https://www.readbyqxmd.com/read/27190130/the-swi3-protein-plays-a-unique-role-in-regulating-respiration-in-eukaryotes
#14
Sneha Lal, Md Maksudul Alam, Jagmohan Hooda, Ajit Shah, Thai M Cao, Zhenyu Xuan, Li Zhang
Recent experimental evidence increasingly shows that the dysregulation of cellular bioenergetics is associated with a wide array of common human diseases, including cancer, neurological diseases and diabetes. Respiration provides a vital source of cellular energy for most eukaryotic cells, particularly high energy demanding cells. However, the understanding of how respiration is globally regulated is very limited. Interestingly, recent evidence suggests that Swi3 is an important regulator of respiration genes in yeast...
July 2016: Bioscience Reports
https://www.readbyqxmd.com/read/26986003/epigenetic-regulation-by-baf-mswi-snf-chromatin-remodeling-complexes-is-indispensable-for-embryonic-development
#15
Huong Nguyen, Godwin Sokpor, Linh Pham, Joachim Rosenbusch, Anastassia Stoykova, Jochen F Staiger, Tran Tuoc
The multi-subunit chromatin-remodeling SWI/SNF (known as BAF for Brg/Brm-associated factor) complexes play essential roles in development. Studies have shown that the loss of individual BAF subunits often affects local chromatin structure and specific transcriptional programs. However, we do not fully understand how BAF complexes function in development because no animal mutant had been engineered to lack entire multi-subunit BAF complexes. Importantly, we recently reported that double conditional knock-out (dcKO) of the BAF155 and BAF170 core subunits in mice abolished the presence of the other BAF subunits in the developing cortex...
May 18, 2016: Cell Cycle
https://www.readbyqxmd.com/read/26952987/the-baf-chromatin-remodelling-complex-is-an-epigenetic-regulator-of-lineage-specification-in-the-early-mouse-embryo
#16
Maryna Panamarova, Andy Cox, Krzysztof B Wicher, Richard Butler, Natalia Bulgakova, Shin Jeon, Barry Rosen, Rho H Seong, William Skarnes, Gerald Crabtree, Magdalena Zernicka-Goetz
Dynamic control of gene expression is essential for the development of a totipotent zygote into an embryo with defined cell lineages. The accessibility of genes responsible for cell specification to transcriptional machinery is dependent on chromatin remodelling complexes such as the SWI\SNF (BAF) complex. However, the role of the BAF complex in early mouse development has remained unclear. Here, we demonstrate that BAF155, a major BAF complex subunit, regulates the assembly of the BAF complex in vivo and regulates lineage specification of the mouse blastocyst...
April 15, 2016: Development
https://www.readbyqxmd.com/read/26655900/loss-of-baf-mswi-snf-complexes-causes-global-transcriptional-and-chromatin-state-changes-in-forebrain-development
#17
Ramanathan Narayanan, Mehdi Pirouz, Cemil Kerimoglu, Linh Pham, Robin J Wagener, Kamila A Kiszka, Joachim Rosenbusch, Rho H Seong, Michael Kessel, Andre Fischer, Anastassia Stoykova, Jochen F Staiger, Tran Tuoc
BAF (Brg/Brm-associated factors) complexes play important roles in development and are linked to chromatin plasticity at selected genomic loci. Nevertheless, a full understanding of their role in development and chromatin remodeling has been hindered by the absence of mutants completely lacking BAF complexes. Here, we report that the loss of BAF155/BAF170 in double-conditional knockout (dcKO) mice eliminates all known BAF subunits, resulting in an overall reduction in active chromatin marks (H3K9Ac), a global increase in repressive marks (H3K27me2/3), and downregulation of gene expression...
December 1, 2015: Cell Reports
https://www.readbyqxmd.com/read/26416882/brg1-governs-nanog-transcription-in-early-mouse-embryos-and-embryonic-stem-cells-via-antagonism-of-histone-h3-lysine-9-14-acetylation
#18
Timothy S Carey, Zubing Cao, Inchul Choi, Avishek Ganguly, Catherine A Wilson, Soumen Paul, Jason G Knott
During mouse preimplantation development, the generation of the inner cell mass (ICM) and trophoblast lineages comprises upregulation of Nanog expression in the ICM and its silencing in the trophoblast. However, the underlying epigenetic mechanisms that differentially regulate Nanog in the first cell lineages are poorly understood. Here, we report that BRG1 (Brahma-related gene 1) cooperates with histone deacetylase 1 (HDAC1) to regulate Nanog expression. BRG1 depletion in preimplantation embryos and Cdx2-inducible embryonic stem cells (ESCs) revealed that BRG1 is necessary for Nanog silencing in the trophoblast lineage...
December 2015: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/26278180/structural-modeling-of-gr-interactions-with-the-swi-snf-chromatin-remodeling-complex-and-c-ebp
#19
Serena Muratcioglu, Diego M Presman, John R Pooley, Lars Grøntved, Gordon L Hager, Ruth Nussinov, Ozlem Keskin, Attila Gursoy
The glucocorticoid receptor (GR) is a steroid-hormone-activated transcription factor that modulates gene expression. Transcriptional regulation by the GR requires dynamic receptor binding to specific target sites located across the genome. This binding remodels the chromatin structure to allow interaction with other transcription factors. Thus, chromatin remodeling is an essential component of GR-mediated transcriptional regulation, and understanding the interactions between these molecules at the structural level provides insights into the mechanisms of how GR and chromatin remodeling cooperate to regulate gene expression...
September 15, 2015: Biophysical Journal
https://www.readbyqxmd.com/read/26257059/nkx6-1-functions-as-a-metastatic-suppressor-through-epigenetic-regulation-of-the-epithelial-mesenchymal-transition
#20
H-J Li, P-N Yu, K-Y Huang, H-Y Su, T-H Hsiao, C-P Chang, M-H Yu, Y-W Lin
The transcription factor NKX6.1 (NK6 homeobox 1) is important in the development of pancreatic β-cells and neurons. Although recent publications show that NKX6.1 is hypermethylated and downregulated during tumorigenesis, the function of NKX6.1 in carcinogenesis remains elusive. Here, we address the metastasis suppressor function of human NKX6.1 using cell, animal and clinical analyses. Our data show that NKX6.1 represses tumor formation and metastatic ability both in vitro and in vivo. Mechanistically, NKX6...
April 28, 2016: Oncogene
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