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https://www.readbyqxmd.com/read/29335648/rapid-chromatin-repression-by-aire-provides-precise-control-of-immune-tolerance
#1
Andrew S Koh, Erik L Miller, Jason D Buenrostro, David M Moskowitz, Jing Wang, William J Greenleaf, Howard Y Chang, Gerald R Crabtree
Aire mediates the expression of tissue-specific antigens in thymic epithelial cells to promote tolerance against self-reactive T lymphocytes. However, the mechanism that allows expression of tissue-specific genes at levels that prevent harm is unknown. Here we show that Brg1 generates accessibility at tissue-specific loci to impose central tolerance. We found that Aire has an intrinsic repressive function that restricts chromatin accessibility and opposes Brg1 across the genome. Aire exerted this repressive influence within minutes after recruitment to chromatin and restrained the amplitude of active transcription...
January 15, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29323272/dominant-negative-smarca4-mutants-alter-the-accessibility-landscape-of-tissue-unrestricted-enhancers
#2
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/29309303/swi-snf-chromatin-remodeling-complex-status-in-smarcb1-ini1-preserved-epithelioid-sarcoma
#3
Kenichi Kohashi, Hidetaka Yamamoto, Yuichi Yamada, Izumi Kinoshita, Tomoaki Taguchi, Yukihide Iwamoto, Yoshinao Oda
The SWI/SNF chromatin-remodeling complex, which is composed of evolutionarily conserved core subunits such as SMARCB1/INI1 (INI1), SMARCA4/BRG1 (BRG1), SMARCC1/BAF155 (BAF155), and SMARCC2/BAF170 (BAF170), can be viewed as the prototype of an epigenetic regulator of gene expression that is involved in tumor suppression. Epithelioid sarcoma, which classified as a tumor of uncertain differentiation, shows an almost complete loss of INI1. However, some cases of epithelioid sarcoma have preserved INI1, and the clinicopathologic features of these cases are uncertain...
January 5, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29290327/-the-value-of-immunohistochemistry-using-smarca4-brg1-in-the-diagnosis-of-small-cell-ovarian-carcinoma-hypercalcemic-type-a-report-of-two-cases
#4
Gema Ruiz-García, M Amparo Torroba-Carón, Belén Ferri-Ñíguez, Miriam Lencina-Guardiola, Francisco García-Molina, Enrique Martínez-Barba
Small cell carcinoma of ovary-hypercalcemic type is an undifferentiated carcinoma. We describe two cases in women aged 32 and 29. Both presented with large masses and complete surgical extirpation was impossible. Histologically, the images were similar, with diffuse cell proliferation, accompanied by the presence of follicle-like spaces. In both cases it was necessary to make a differential diagnosis with entities such as adult or juvenile granulosa cell tumour, small cell carcinoma of pulmonary type, dysgerminoma and even peripheral neuroectodermal tumour...
January 2018: Revista Española de Patología
https://www.readbyqxmd.com/read/29288038/brg1-is-correlated-with-poor-prognosis-in-colorectal-cancer
#5
Jung-Soo Pyo, Byoung Kwan Son, Dongwook Oh, Eun Kyung Kim
Brahma-related gene 1 (BRG1), a component of the chromatin-remodeling complex, regulates transcription by remodeling the chromatin structure. The present study aimed to elucidate the clinicopathological significance and prognostic role of BRG1 in colorectal cancer (CRC). We investigated the correlation between BRG1 expression and clinicopathological parameters, including prognosis, using immunohistochemistry on 266 archival paraffin-embedded CRC tissues. In addition, to confirm the prognostic role of BRG1 in malignant tumors, we performed a meta-analysis of nine eligible studies and the current study...
December 26, 2017: Human Pathology
https://www.readbyqxmd.com/read/29273066/co-regulation-of-transcription-by-brg1-and-brm-two-mutually-exclusive-swi-snf-atpase-subunits
#6
Jesse R Raab, John S Runge, Camarie C Spear, Terry Magnuson
BACKGROUND: SWI/SNF is a large heterogeneous multi-subunit chromatin remodeling complex. It consists of multiple sets of mutually exclusive components. Understanding how loss of one sibling of a mutually exclusive pair affects the occupancy and function of the remaining complex is needed to understand how mutations in a particular subunit might affect tumor formation. Recently, we showed that the members of the ARID family of SWI/SNF subunits (ARID1A, ARID1B and ARID2) had complex transcriptional relationships including both antagonism and cooperativity...
December 22, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29260792/a-novel-role-for-oligodendrocyte-precursor-cells-opcs-and-sox10-in-mediating-cellular-and-behavioral-responses-to-heroin
#7
Jennifer A Martin, Aaron Caccamise, Craig T Werner, Rathipriya Viswanathan, Jessie J Polanco, Andrew F Stewart, Shruthi A Thomas, Fraser J Sim, David M Dietz
Opiate abuse and addiction have become a worldwide epidemic with great societal and financial burdens, highlighting a critical need to understand the neurobiology of opiate addiction. While several studies have focused on drug-dependent changes in neurons, the role of glia in opiate addiction remains largely unstudied. RNA sequencing pathway analysis from the prefrontal cortex of male rats revealed changes in several genes associated with oligodendrocyte differentiation and maturation following heroin self-administration...
December 20, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29142070/gfap-and-osmr-regulation-by-brg1-and-stat3-via-interchromosomal-gene-clustering-in-astrocytes
#8
Kenji Ito, Azumi Noguchi, Yuichi Uosaki, Testuya Taga, Hirokazu Arakawa, Takumi Takizawa
Long-range chromatin interactions between gene loci in the cell nucleus are important for many biological processes including transcriptional regulation. Previously, we demonstrated that several genes specifically cluster with the astrocyte-specific gene glial fibrillary acidic protein (Gfap) during astrocyte differentiation; however, the molecular mechanisms for gene clustering remain largely unknown. Here we show that brahma-related gene 1 (BRG1), an ATP-dependent chromatin remodeling factor, and the transcription factor STAT3 are required for Gfap and Osmr clustering and enhanced expression through recruitment to STAT3 recognition sequences and that gene clustering occurs prior to transcriptional upregulation...
November 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29132471/-oridonin-inhibits-proliferation-of-jurkat-cells-via-the-down-regulation-of-brg1
#9
Zhen-Zhen Ye, Fei-Long Xue, Wen-Ping Ding, Xiang Kong, Yi-Na Shen
OBJECTIVE: To investigate the effect of oridonin on the human acute lymphocytic leukemia cell line Jurkat and its mechanism. METHODS: Jurkat cells were cultured in vitro and treated with various concentrations (0, 1.25, 2.5, 5, and 10 μmol/L) of oridonin for different lengths of time (24, 48, and 72 hours). The proliferation of Jurkat cells was analyzed by MTT assay. The changes in nuclear morphology were evaluated by fluorescence microscopy at 12 hours after treatment with various concentrations of oridonin...
November 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/29126175/conventional-and-pioneer-modes-of-glucocorticoid-receptor-interaction-with-enhancer-chromatin-in-vivo
#10
Thomas A Johnson, Razvan V Chereji, Diana A Stavreva, Stephanie A Morris, Gordon L Hager, David J Clark
Glucocorticoid hormone plays a major role in metabolism and disease. The hormone-bound glucocorticoid receptor (GR) binds to a specific set of enhancers in different cell types, resulting in unique patterns of gene expression. We have addressed the role of chromatin structure in GR binding by mapping nucleosome positions in mouse adenocarcinoma cells. Before hormone treatment, GR-enhancers exist in one of three chromatin states: (i) Nucleosome-depleted enhancers that are DNase I-hypersensitive, associated with the Brg1 chromatin remodeler and flanked by nucleosomes incorporating histone H2A...
November 8, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29109331/mkl1-mediates-tnf-%C3%AE-induced-pro-inflammatory-transcription-by-bridging-the-crosstalk-between-brg1-and-wdr5
#11
Wenping Xu, Quanyi Zhao, Min Wu, Mingming Fang, Yong Xu
Tumor necrosis factor alpha (TNF-α) is a cytokine that can potently stimulate the synthesis of a range of pro-inflammatory mediators in macrophages. The underlying epigenetic mechanism, however, is underexplored. Here we report that the transcriptional modulator megakaryocytic leukemia 1 (MKL1) is associated with a histone H3K4 methyltransferase activity. Re-ChIP assay suggests that MKL1 interacts with and recruits WDR5, a component of the COMPASS complex responsible for H3K4 methylation, to the promoter regions of pro-inflammatory genes in macrophages treated with TNF-α...
November 1, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/29101221/%C3%AE-actin-dependent-global-chromatin-organization-and-gene-expression-programs-control-cellular-identity
#12
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...
November 3, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29070872/baf53a-is-involved-in-survival-of-mouse-es-cells-which-can-be-compensated-by-baf53b
#13
Bo Zhu, Atsushi Ueda, Xiaohong Song, Shin-Ichi Horike, Takashi Yokota, Tadayuki Akagi
The human Baf (Brg1/Brm associated factor) complex, also known as the mammalian SWI/SNF chromatin-remodeling complex, is involved in a variety of cellular processes. The pluripotency and self-renewal abilities are major characteristics of embryonic stem (ES) cells and are regulated by the ES cell-specific BAF (esBAF) complex. Baf53a is one of the subunits of the esBAF complex. Here, we found that Baf53a was expressed in undifferentiated ES cells and that it interacted with Oct3/4. Analyses of tetracycline-inducible Baf53a conditional knockout ES cells revealed that the undifferentiated markers, including Nanog and Oct3/4, were expressed in Baf53a-deficient ES cells; however, growth of the cells was repressed, and expression of p53, p21, and cleaved Caspase 3 was increased...
October 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29042984/bmi1-and-brg1-drive-myocardial-repair-by-regulating-cardiac-stem-cell-function-in-acute-rheumatic-heart-disease
#14
Pingxi Xiao, Kai Zhang, Zhiwen Tao, Niannian Liu, Bangshun Ge, Min Xu, Xinzheng Lu
Rheumatic heart disease (RHD) occurs due to the accumulation of complications associated with rheumatic fever, and it results in high morbidity and mortality. The majority of cases of RHD are diagnosed in the chronic stages, when treatment options are limited. A small reservoir of cardiac stem cells is responsible for maintaining cardiac homeostasis and repairing tissue damage. Understanding the role of cardiac stem cells and the various proteins responsible for their functions in different pathological stages of RHD is an important area of investigation...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28973294/dysregulation-of-chromatin-remodelling-complexes-in-amyotrophic-lateral-sclerosis
#15
Michael Tibshirani, Beibei Zhao, Benoit J Gentil, Sandra Minotti, Christine Marques, Julia Keith, Ekaterina Rogaeva, Lorne Zinman, Caroline Rouaux, Janice Robertson, Heather D Durham
Amyotrophic lateral sclerosis is a fatal neurodegenerative disease with paralysis resulting from dysfunction and loss of motor neurons. A common neuropathological finding is attrition of motor neuron dendrites, which make central connections vital to motor control. The chromatin remodelling complex, neuronal Brahma-related gene 1 (Brg1)-associated factor complex (nBAF), is critical for neuronal differentiation, dendritic extension and synaptic function. We have identified loss of the crucial nBAF subunits Brg1, Brg1-associated factor 53b and calcium responsive transactivator in cultured motor neurons expressing FUS or TAR-DNA Binding Protein 43 (TDP-43) mutants linked to familial ALS...
November 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28961249/swi-snf-infobase-an-exclusive-information-portal-for-swi-snf-remodeling-complex-subunits
#16
Udayakumar Mani, Alagu Sankareswaran S, Arun Goutham R N, Suma Mohan S
Chromatin remodeling complexes facilitate the access of condensed genomic DNA during transcription, replication, and repair, by altering the histone-DNA contacts in the nucleosome structures. SWI/SNF (SWItch/Sucrose Non-Fermentable) family of ATP dependent chromatin remodeling complexes have been documented for their tumour suppressor function. Recent studies have reported the high frequency of cancer causing mutations in this protein family. There exist multiple subunits for this complex and can form context-dependent sub-complexes...
2017: PloS One
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
#17
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/28903392/a-role-for-brg1-in-the-regulation-of-genes-required-for-development-of-the-lymphatic-system
#18
Ajeet Pratap Singh, Julie Foley, Arpit Tandon, Dhiral Phadke, H Karimi Kinyamu, Trevor K Archer
Lymphatic vasculature is an important part of the cardiovascular system with multiple functions, including regulation of the return of interstitial fluid (lymph) to the bloodstream, immune responses, and fat absorption. Consequently, lymphatic vasculature defects are involved in many pathological processes, including tumor metastasis and lymphedema. BRG1 is an important player in the developmental window when the lymphatic system is initiated. In the current study, we used tamoxifen inducible Rosa26CreERT2-BRG1(floxed/floxed) mice that allowed temporal analysis of the impact of BRG1 inactivation in the embryo...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28899659/brg1-promotes-vegf-a-expression-and-angiogenesis-in-human-colorectal-cancer-cells
#19
Jingqin Lan, Haijie Li, Xuelai Luo, Junbo Hu, Guihua Wang
Angiogenesis plays an important role in tumor growth and progression in solid tumors. Vascular endothelial growth factor (VEGF) is one of the most critical and specific factors that stimulate both physiological and pathological angiogenesis. Here, we report a novel role of BRG1, the core subunit of SWI/SNF family complexes, in angiogenesis. In this study, we demonstrate that BRG1 is overexpressed in colorectal cancer and decreased expression of BRG1 not only blocks cell proliferation but remarkably inhibits the ability of HUVECs to form capillary-like structures...
November 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28863138/5c-analysis-of-the-epidermal-differentiation-complex-locus-reveals-distinct-chromatin-interaction-networks-between-gene-rich-and-gene-poor-tads-in-skin-epithelial-cells
#20
Krzysztof Poterlowicz, Joanne L Yarker, Igor Malashchuk, Brian R Lajoie, Andrei N Mardaryev, Michal R Gdula, Andrey A Sharov, Terumi Kohwi-Shigematsu, Vladimir A Botchkarev, Michael Y Fessing
Mammalian genomes contain several dozens of large (>0.5 Mbp) lineage-specific gene loci harbouring functionally related genes. However, spatial chromatin folding, organization of the enhancer-promoter networks and their relevance to Topologically Associating Domains (TADs) in these loci remain poorly understood. TADs are principle units of the genome folding and represents the DNA regions within which DNA interacts more frequently and less frequently across the TAD boundary. Here, we used Chromatin Conformation Capture Carbon Copy (5C) technology to characterize spatial chromatin interaction network in the 3...
September 2017: PLoS Genetics
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