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https://www.readbyqxmd.com/read/28431046/brg1-interacts-with-sox10-to-establish-the-melanocyte-lineage-and-to-promote-differentiation
#1
Himangi G Marathe, Dawn E Watkins-Chow, Matthias Weider, Alana Hoffmann, Gaurav Mehta, Archit Trivedi, Shweta Aras, Tupa Basuroy, Aanchal Mehrotra, Dorothy C Bennett, Michael Wegner, William J Pavan, Ivana L de la Serna
Mutations in SOX10 cause neurocristopathies which display varying degrees of hypopigmentation. Using a sensitized mutagenesis screen, we identified Smarca4 as a modifier gene that exacerbates the phenotypic severity of Sox10 haplo-insufficient mice. Conditional deletion of Smarca4 in SOX10 expressing cells resulted in reduced numbers of cranial and ventral trunk melanoblasts. To define the requirement for the Smarca4 -encoded BRG1 subunit of the SWI/SNF chromatin remodeling complex, we employed in vitro models of melanocyte differentiation in which induction of melanocyte-specific gene expression is closely linked to chromatin alterations...
April 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28428261/ebf2-transcriptionally-regulates-brown-adipogenesis-via-the-histone-reader-dpf3-and-the-baf-chromatin-remodeling-complex
#2
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 20, 2017: Genes & Development
https://www.readbyqxmd.com/read/28421159/mammalian-swi-snf-enzymes-and-the-epigenetics-of-tumor-cell-metabolic-reprogramming
#3
REVIEW
Jeffrey A Nickerson, Qiong Wu, Anthony N Imbalzano
Tumor cells reprogram their metabolism to survive and grow in a challenging microenvironment. Some of this reprogramming is performed by epigenetic mechanisms. Epigenetics is in turn affected by metabolism; chromatin modifying enzymes are dependent on substrates that are also key metabolic intermediates. We have shown that the chromatin remodeling enzyme Brahma-related gene 1 (BRG1), an epigenetic regulator, is necessary for rapid breast cancer cell proliferation. The mechanism for this requirement is the BRG1-dependent transcription of key lipogenic enzymes and regulators...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28417598/genetic-analysis-of-a-morphologically-heterogeneous-ovarian-endometrioid-carcinoma
#4
Felipe C Geyer, Fresia Pareja, Kathleen A Burke, Anne M Schultheis, Yaser R Hussein, Jiqing Ye, Maria R De Filippo, Caterina Marchio, Gabriel S Macedo, Salvatore Piscuoglio, Raymond S Lim, Eugene Toy, Rajmohan Murali, Achim A Jungbluth, Jorge S Reis-Filho, Robert A Soslow, Britta Weigelt
AIMS: Low-grade ovarian endometrioid carcinomas may be associated with high-grade components. Whether the latter are clonally-related to and originate from the low-grade endometrioid carcinoma remains unclear. Here we employed massively parallel sequencing to characterize the genomic landscape and clonal relatedness of an ovarian endometrioid carcinoma containing low- and high-grade components. METHODS AND RESULTS: DNA samples extracted from each tumor component (low-grade endometrioid, high-grade anaplastic, high-grade squamous) and matched normal tissue were subjected to targeted massively parallel sequencing using the 410 gene Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) sequencing assay...
April 18, 2017: Histopathology
https://www.readbyqxmd.com/read/28416631/mutation-of-neuron-specific-chromatin-remodeling-subunit-baf53b-rescue-of-plasticity-and-memory-by-manipulating-actin-remodeling
#5
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/28385531/mkl1-links-epigenetic-activation-of-mmp2-to-ovarian-cancer-cell-migration-and-invasion
#6
Mingzi Song, Huihui Xu, Mingming Fang, Xiaoyan Wu, Yong Xu
Responding to pro-metastatic cues such as low oxygen tension, cancer cells develop several different strategies to facilitate migration and invasion. During this process, expression levels of matrix metalloproteinases (MMPs) are up-regulated so that cancer cells can more easily enter or exit the circulation. In this report we show that message levels of the transcriptional modulator MKL1 were elevated in malignant forms of ovarian cancer tissues in humans when compared to more benign forms accompanying a similar change in MMP2 expression...
April 3, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28381560/the-chromatin-remodeling-subunit-baf200-promotes-homology-directed-dna-repair-and-regulates-distinct-chromatin-remodeling-complexes
#7
Rodrigo O de Castro, Luciana Previato, Victor Goitea, Anna Felberg, Michael 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...
April 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28369036/chromatin-remodeling-factor-smarcd2-regulates-transcriptional-networks-controlling-differentiation-of-neutrophil-granulocytes
#8
Maximilian Witzel, Daniel Petersheim, Yanxin Fan, Ehsan Bahrami, Tomas Racek, Meino Rohlfs, Jacek Puchałka, Christian Mertes, Julien Gagneur, Christoph Ziegenhain, Wolfgang Enard, Asbjørg Stray-Pedersen, Peter D Arkwright, Miguel R Abboud, Vahid Pazhakh, Graham J Lieschke, Peter M Krawitz, Maik Dahlhoff, Marlon R Schneider, Eckhard Wolf, Hans-Peter Horny, Heinrich Schmidt, Alejandro A Schäffer, Christoph Klein
We identify SMARCD2 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily D, member 2), also known as BAF60b (BRG1/Brahma-associated factor 60b), as a critical regulator of myeloid differentiation in humans, mice, and zebrafish. Studying patients from three unrelated pedigrees characterized by neutropenia, specific granule deficiency, myelodysplasia with excess of blast cells, and various developmental aberrations, we identified three homozygous loss-of-function mutations in SMARCD2...
April 3, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28351900/long-noncoding-rna-mantis-facilitates-endothelial-angiogenic-function
#9
Matthias S Leisegang, Christian Fork, Ivana Josipovic, Florian Richter, Jens Preussner, Jiong Hu, Matthew J Miller, Jeremy N Epah, Patrick Hofmann, Stefan Günther, Franziska Moll, Chanil Valasarajan, Juliana Heidler, Yuliya Ponomareva, Thomas M Freiman, Lars Maegdefessel, Karl H Plate, Michel Mittelbronn, Shizuka Uchida, Carsten Künne, Konstantinos Stellos, Ralph T Schermuly, Norbert Weissmann, Kavi Devraj, Ilka Wittig, Reinier A Boon, Stefanie Dimmeler, Soni S Pullamsetti, Mario Looso, Francis J Miller, Ralf P Brandes
Background -The angiogenic function of endothelial cells is regulated by numerous mechanisms but the impact of long noncoding RNAs (lncRNAs) has hardly been studied. We set out to identify novel and functionally important endothelial lncRNAs. Methods -Epigenetically controlled lncRNAs in human umbilical vein endothelial cells (HUVEC) were searched by exon-array analysis after knockdown of the histone demethylase JARID1B. Molecular mechanisms were investigated by RNA Pulldown and Immunoprecipitation, Mass spectrometry, Micro-array, several knockdown approaches, CRIPSR-Cas9, Assay for Transposase-Accessible Chromatin-Sequencing and chromatin immunoprecipitation in HUVEC...
March 28, 2017: Circulation
https://www.readbyqxmd.com/read/28287392/the-pioneer-factor-oct4-requires-the-chromatin-remodeller-brg1-to-support-gene-regulatory-element-function-in-mouse-embryonic-stem-cells
#10
Hamish W King, Robert J Klose
Pioneer transcription factors recognise and bind their target sequences in inaccessible chromatin to establish new transcriptional networks throughout development and cellular reprogramming. During this process, pioneer factors establish an accessible chromatin state to facilitate additional transcription factor binding, yet it remains unclear how different pioneer factors achieve this. Here, we discover that the pluripotency-associated pioneer factor OCT4 binds chromatin to shape accessibility, transcription factor co-binding, and regulatory element function in mouse embryonic stem cells...
March 13, 2017: ELife
https://www.readbyqxmd.com/read/28251496/brg1-regulation-by-mir-155-in-human-leukemia-and-lymphoma-cell-lines
#11
M Cuadros, V Sánchez-Martín, A Herrera, C Baliñas, J Martín-Padrón, L Boyero, P Peinado, P P Medina
INTRODUCTION/PURPOSE: BRG1 is a key regulator of leukemia stem cells. Indeed, it has been observed that this type of cells is unable to divide, survive and develop new tumors when BRG1 is down-regulated. MATERIALS AND METHODS: We assessed BRG1 and miR-155 expression in 23 leukemia cell lines, and two no pathological lymphocyte samples using qPCR. MiR-155 transfection and western blot were used to analyze the relationship between miR-155 and its validated target, BRG1, by measuring protein expression levels...
March 1, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28236308/prmt5-restricts-hepatitis-b-virus-replication-via-epigenetic-repression-of-cccdna-transcription-and-interference-with-pgrna-encapsidation
#12
Wen Zhang, Jieliang Chen, Min Wu, Xiaonan Zhang, Min Zhang, Lei Yue, Yaming Li, Jiangxia Liu, Baocun Li, Fang Shen, Yang Wang, Lu Bai, Ulrike Protzer, Massimo Levrero, Zhenghong Yuan
Chronic hepatitis B virus (HBV) infection remains a major health problem worldwide. The covalently closed circular DNA (cccDNA) minichromosome, which serves as the template for the transcription of viral RNAs, plays a key role in viral persistence. While accumulating evidence suggests that cccDNA transcription is regulated by epigenetic machinery, particularly the acetylation of cccDNA-bound histone 3 (H3) and H4, the potential contributions of histone methylation and related host factors remain obscured. Here, by screening a series of methyltransferases and demethylases, we identified protein arginine methyltransferase 5 (PRMT5) as an effective restrictor of HBV transcription and replication...
February 25, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28228591/the-swi-snf-chromatin-regulator-brg1-modulates-the-transcriptional-regulatory-activity-of-the-ebv-dna-polymerase-processivity-factor-bmrf1
#13
Mei-Tzu Su, Ya-Ting Wang, Yen-Ju Chen, Su-Fang Lin, Ching-Hwa Tsai, Mei-Ru Chen
During lytic phase of Epstein-Barr virus (EBV), binding of the transactivator Zta to the origin of lytic replication (oriLyt) and the BHLF1 transcript, forming a stable RNA-DNA hybrid, are required to initiate viral DNA replication. EBV-encoded viral DNA replication proteins form complexes to amplify viral DNA. BMRF1, the viral DNA polymerase accessory factor, is essential for lytic DNA replication and also known as a transcriptional regulator of the expression of BHLF1 and BALF2 (ssDNA-binding protein). In order to determine systematically how BMRF1 regulates viral transcription, a BMRF1 knockout bacmid was generated to analyze viral gene expression using a viral DNA microarray...
February 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28203701/integrative-analysis-identifies-co-dependent-gene-expression-regulation-of-brg1-and-chd7-at-distal-regulatory-sites-in-embryonic-stem-cells
#14
Pengyi Yang, Andrew Oldfield, Taiyun Kim, Andrian Yang, Jean Yee Hwa Yang, Joshua W K Ho
No abstract text is available yet for this article.
February 14, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28202515/systematic-in-vivo-inactivation-of-chromatin-regulating-enzymes-identifies-setd2-as-a-potent-tumor-suppressor-in-lung-adenocarcinoma
#15
David M Walter, Olivia S Venancio, Elizabeth L Buza, John W Tobias, Charuhas Deshpande, A Andrea Gudiel, Caroline Kim-Kiselak, Michelle Cicchini, Travis J Yates, David M Feldser
Chromatin-modifying genes are frequently mutated in human lung adenocarcinoma, but the functional impact of these mutations on disease initiation and progression is not well understood. Using a CRISPR-based approach, we systematically inactivated three of the most commonly mutated chromatin regulatory genes in two Kras(G12D)-driven mouse models of lung adenocarcinoma to characterize the impact of their loss. Targeted inactivation of SWI/SNF nucleosome-remodeling complex members Smarca4 (Brg1) or Arid1a had complex effects on lung adenocarcinoma initiation and progression...
April 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28193841/dual-roles-of-akirin2-protein-during-xenopus-neural-development
#16
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
https://www.readbyqxmd.com/read/28182012/loss-of-brg1-induces-crc-cell-senescence-by-regulating-p53-p21-pathway
#17
Guihua Wang, Yinjia Fu, Fuqing Hu, Jinqing Lan, Feng Xu, Xi Yang, Xuelai Luo, Jing Wang, Junbo Hu
Brahma-related gene-1 (BRG1) is the specific ATPase of switch/sucrose nonfermentable chromatin-remodeling complex that is aberrantly expressed or mutated in various cancers. However, the exact role of BRG1 in oncogenesis remains unknown. In this study, we demonstrate that the knockdown (KD) of BRG1 promotes cellular senescence by influencing the SIRT1/p53/p21 signal axis in colorectal cancer (CRC). In particular, we reveal that the expression level of BRG1 is inversely correlated with p21, one of the classic senescence regulators, and is decreased in senescent CRC cells...
February 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28102363/smarca4-inactivating-mutations-increase-sensitivity-to-aurora-kinase-a-inhibitor-vx-680-in-non-small-cell-lung-cancers
#18
Vural Tagal, Shuguang Wei, Wei Zhang, Rolf A Brekken, Bruce A Posner, Michael Peyton, Luc Girard, TaeHyun Hwang, David A Wheeler, John D Minna, Michael A White, Adi F Gazdar, Michael G Roth
Mutations in the SMARCA4/BRG1 gene resulting in complete loss of its protein (BRG1) occur frequently in non-small cell lung cancer (NSCLC) cells. Currently, no single therapeutic agent has been identified as synthetically lethal with SMARCA4/BRG1 loss. We identify AURKA activity as essential in NSCLC cells lacking SMARCA4/BRG1. In these cells, RNAi-mediated depletion or chemical inhibition of AURKA induces apoptosis and cell death in vitro and in xenograft mouse models. Disc large homologue-associated protein 5 (HURP/DLGAP5), required for AURKA-dependent, centrosome-independent mitotic spindle assembly is essential for the survival and proliferation of SMARCA4/BRG1 mutant but not of SMARCA4/BRG1 wild-type cells...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28091529/long-non-coding-rna-linc-ram-enhances-myogenic-differentiation-by-interacting-with-myod
#19
Xiaohua Yu, Yong Zhang, Tingting Li, Zhao Ma, Haixue Jia, Qian Chen, Yixia Zhao, Lili Zhai, Ran Zhong, Changyin Li, Xiaoting Zou, Jiao Meng, Antony K Chen, Pier Lorenzo Puri, Meihong Chen, Dahai Zhu
Long non-coding RNAs (lncRNAs) are important regulators of diverse biological processes. Here we report on functional identification and characterization of a novel long intergenic non-coding RNA with MyoD-regulated and skeletal muscle-restricted expression that promotes the activation of the myogenic program, and is therefore termed Linc-RAM (Linc-RNA Activator of Myogenesis). Linc-RAM is transcribed from an intergenic region of myogenic cells and its expression is upregulated during myogenesis. Notably, in vivo functional studies show that Linc-RAM knockout mice display impaired muscle regeneration due to the differentiation defect of satellite cells...
January 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28060558/the-connection-between-brg1-ctcf-and-topoisomerases-at-tad-boundaries
#20
A Rasim Barutcu, Jane B Lian, Janet L Stein, Gary S Stein, Anthony N Imbalzano
The eukaryotic genome is partitioned into topologically associating domains (TADs). Despite recent advances characterizing TADs and TAD boundaries, the organization of these structures is an important dimension of genome architecture and function that is not well understood. Recently, we demonstrated that knockdown of BRG1, an ATPase driving the chromatin remodeling activity of mammalian SWI/SNF enzymes, globally alters long-range genomic interactions and results in a reduction of TAD boundary strength. We provided evidence suggesting that this effect may be due to BRG1 affecting nucleosome occupancy around CTCF sites present at TAD boundaries...
March 4, 2017: Nucleus
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