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https://www.readbyqxmd.com/read/27914010/recruitment-by-the-repressor-freud-1-of-histone-deacetylase-brg1-chromatin-remodeling-complexes-to-strengthen-htr1a-gene-repression
#1
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 2, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27905400/lncbrm-initiates-yap1-signalling-activation-to-drive-self-renewal-of-liver-cancer-stem-cells
#2
Pingping Zhu, Yanying Wang, Jiayi Wu, Guanling Huang, Benyu Liu, Buqing Ye, Ying Du, Guangxia Gao, Yong Tian, Lei He, Zusen Fan
Liver cancer stem cells (CSCs) may contribute to the high rate of recurrence and heterogeneity of hepatocellular carcinoma (HCC). However, the biology of hepatic CSCs remains largely undefined. Through analysis of transcriptome microarray data, we identify a long noncoding RNA (lncRNA) called lncBRM, which is highly expressed in liver CSCs and HCC tumours. LncBRM is required for the self-renewal maintenance of liver CSCs and tumour initiation. In liver CSCs, lncBRM associates with BRM to initiate the BRG1/BRM switch and the BRG1-embedded BAF complex triggers activation of YAP1 signalling...
December 1, 2016: Nature Communications
https://www.readbyqxmd.com/read/27879032/altered-expression-of-brg1-and-histone-demethylases-and-aberrant-h3k4-methylation-in-less-developmentally-competent-embryos-at-the-time-of-embryonic-genome-activation
#3
W G Glanzner, A Wachter, A R S Coutinho, M S Albornoz, R Duggavathi, P B D Gonçalves, V Bordignon
Epigenetics is a fundamental regulator underlying many biological functions, such as development and cell differentiation. Epigenetic modifications affect key chromatin regulation, including transcription and DNA repair, which are critical for normal embryo development. In this study, we profiled the expression of epigenetic modifiers and patterns of epigenetic changes in porcine embryos around the period of embryonic genome activation (EGA). We observed that Brahma-related gene 1 (BRG1) and Lysine demethylase 1A (KDM1A), which can alter the methylation status of lysine 4 in histone 3 (H3K4), localize to the nucleus at Days 3-4 of development...
November 23, 2016: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/27852072/the-chromatin-remodeling-enzyme-brg1-promotes-colon-cancer-progression-via-positive-regulation-of-wnt3a
#4
Shengtao Lin, Tao Jiang, Ling Ye, Zhongbo Han, Yuan Liu, Chenchen Liu, Chenwei Yuan, Senlin Zhao, Jian Chen, Jingtao Wang, Huamei Tang, Su Lu, Liguang Yang, Xiaoliang Wang, Dongwang Yan, Zhihai Peng, Junwei Fan
In this study, we aimed to elucidate the clinical significance and underlying mechanisms of BRG1 in colon cancer. In the clinical analysis, overexpression of BRG1 correlates with colon cancer progression in two cohorts (n = 191 and n = 75). Kaplan-Meier survival analysis revealed that BRG1 is a prognosis predictor for overall survival (P < 0.001) and disease-free survival (P = 0.001). Knocking down BRG1 expression significantly suppressed the proliferation and invasion in colon cancer cells. The expression pattern of WNT3A is consistent with BRG1 in colon cancer tissues and WNT3A expression was inhibited in BRG1 knockdown cells...
November 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27797380/dna-demethylation-induces-sall4-gene-re-expression-in-subgroups-of-hepatocellular-carcinoma-associated-with-hepatitis-b-or-c-virus-infection
#5
H Fan, Z Cui, H Zhang, S K Mani, A Diab, L Lefrancois, N Fares, P Merle, O Andrisani
Sal-like protein 4 (SALL4), an embryonic stem cell transcriptional regulator, is re-expressed by an unknown mechanism in poor prognosis hepatocellular carcinoma (HCC), often associated with chronic hepatitis B virus (HBV) infection. Herein, we investigated the mechanism of SALL4 re-expression in HBV-related HCCs. We performed bisulfite sequencing PCR of genomic DNA isolated from HBV-related HCCs and HBV replicating cells, and examined DNA methylation of a CpG island located downstream from SALL4 transcriptional start site (TSS)...
October 31, 2016: Oncogene
https://www.readbyqxmd.com/read/27764136/immunohistochemistry-successfully-uncovers-intratumoral-heterogeneity-and-widespread-co-losses-of-chromatin-regulators-in-clear-cell-renal-cell-carcinoma
#6
Wei Jiang, Essel Dulaimi, Karthik Devarajan, Theodore Parsons, Qiong Wang, Lili Liao, Eun-Ah Cho, Raymond O'Neill, Charalambos Solomides, Stephen C Peiper, Joseph R Testa, Robert Uzzo, Haifeng Yang
Recent studies have shown that intratumoral heterogeneity (ITH) is prevalent in clear cell renal cell carcinoma (ccRCC), based on DNA sequencing and chromosome aberration analysis of multiple regions from the same tumor. VHL mutations were found to be universal throughout individual tumors when it occurred (ubiquitous), while the mutations in other tumor suppressor genes tended to be detected only in parts of the tumors (subclonal). ITH has been studied mostly by DNA sequencing in limited numbers of samples, either by whole genome sequencing or by targeted sequencing...
2016: PloS One
https://www.readbyqxmd.com/read/27736764/beauvericin-potentiates-azole-activity-via-inhibition-of-multidrug-efflux-blocks-c-albicans-morphogenesis-and-is-effluxed-via-yor1-and-circuitry-controlled-by-zcf29
#7
Tanvi Shekhar-Guturja, Walters Aji Tebung, Harley Mount, Ningning Liu, Julia R Köhler, Malcolm Whiteway, Leah E Cowen
Invasive fungal infections are a leading cause of human mortality. Effective treatment is hindered by the rapid emergence of resistance to the limited number of antifungal drugs, demanding new strategies to treat life-threatening fungal infections. Here, we explore a powerful strategy to enhance antifungal efficacy using the natural product beauvericin against leading human fungal pathogens. We found that beauvericin potentiates the activity of azole antifungals against azole-resistant Candida isolates via inhibition of multidrug efflux, and that beauvericin itself is effluxed via Yor1...
October 10, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27700223/steroid-hormone-receptors-silence-genes-by-a-chromatin-targeted-mechanism-similar-to-those-used-for-gene-activation
#8
A Silvina Nacht, Miguel Beato, Guillermo P Vicent
How genes are repressed by steroid hormones remains a matter of debate and several indirect mechanisms have been proposed. We found that the ligand-activated progesterone receptor (PR) recruits to the promoter of down-regulated genes a repressor complex composed of HP1γ, the lysine demethylase LSD1, histone deacetylases, coREST, the RNA SRA and the ATPase BRG1. BRG1 is needed for chromatin remodeling and facilitates the deposition of linker histone variant H1.2, which compacts chromatin and hinders RNA polymerase loading and transcription...
October 4, 2016: Transcription
https://www.readbyqxmd.com/read/27697157/chromatin-remodeling-in-addiction-brg1-smad3-interaction-contributes-to-cued-reinstatement-of-cocaine-seeking
#9
Alexander C W Smith
No abstract text is available yet for this article.
November 1, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/27695363/atypical-teratoid-rhabdoid-tumors-challenges-and-search-for-solutions
#10
Ahitagni Biswas, Lakhan Kashyap, Aanchal Kakkar, Chitra Sarkar, Pramod Kumar Julka
Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant embryonal central nervous system tumor commonly affecting children <3 years of age. It roughly constitutes 1%-2% of all pediatric central nervous system tumors. Recent data show that it is the most common malignant central nervous system tumor in children <6 months of age. Management of this aggressive tumor is associated with a myriad of diagnostic and therapeutic challenges. On the basis of radiology and histopathology alone, distinction of AT/RT from medulloblastoma or primitive neuroectodermal tumor is difficult, and hence this tumor has been commonly misdiagnosed as primitive neuroectodermal tumor for decades...
2016: Cancer Management and Research
https://www.readbyqxmd.com/read/27695031/metal-chelation-as-a-powerful-strategy-to-probe-cellular-circuitry-governing-fungal-drug-resistance-and-morphogenesis
#11
Elizabeth J Polvi, Anna F Averette, Soo Chan Lee, Taeyup Kim, Yong-Sun Bahn, Amanda O Veri, Nicole Robbins, Joseph Heitman, Leah E Cowen
Fungal pathogens have evolved diverse strategies to sense host-relevant cues and coordinate cellular responses, which enable virulence and drug resistance. Defining circuitry controlling these traits opens new opportunities for chemical diversity in therapeutics, as the cognate inhibitors are rarely explored by conventional screening approaches. This has great potential to address the pressing need for new therapeutic strategies for invasive fungal infections, which have a staggering impact on human health...
October 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27630343/increased-brahma-related-gene-1-expression-predicts-distant-metastasis-and-shorter-survival-in-patients-with-invasive-ductal-carcinoma-of-the-breast
#12
Sung-Im DO, Gun Yoon, Hyun-Soo Kim, Kyungeun Kim, Hyunjoo Lee, In-Gu DO, Dong-Hoon Kim, Seoung Wan Chae, Jin Hee Sohn
BACKGROUND: Previous studies have demonstrated aberrant Brahma-related gene 1 (BRG1) expression in various tumor types. Increased BRG1 expression has recently been shown to correlate with aggressive oncogenic behavior in many different types of human cancer. However, the role of BRG1 in breast cancer development and progression is not fully understood. MATERIALS AND METHODS: We evaluated BRG1 expression in 224 patients with invasive ductal carcinoma (IDC) of the breast using tissue microarray samples and immunohistochemistry...
September 2016: Anticancer Research
https://www.readbyqxmd.com/read/27605510/microrna-139-5p-regulates-proliferation-of-hematopoietic-progenitors-and-is-repressed-during-bcr-abl-mediated-leukemogenesis
#13
Jinwook Choi, Young-Kook Kim, Kyungsoo Park, Jinwoo Nah, Sung-Soo Yoon, Dong-Wook Kim, V Narry Kim, Rho Hyun Seong
MicroRNAs (miRNAs) have emerged as important regulators of the immune system. However, despite this prominence, our understanding of the function of miRNAs in the early hematopoietic stages is incomplete. In this study, we found that miR-139-5p negatively regulated the proliferation of hematopoietic stem cells and progenitor cells and that downregulation of miR-139-5p expression was associated with hematopoietic malignancy, such as chronic myeloid leukemia (CML). Knockdown of miR-139-5p resulted in myeloid-biased differentiation with expansion of myeloid progenitor cells...
October 27, 2016: Blood
https://www.readbyqxmd.com/read/27601681/pathological-ace2-to-ace-enzyme-switch-in-the-stressed-heart-is-transcriptionally-controlled-by-the-endothelial-brg1-foxm1-complex
#14
Jin Yang, Xuhui Feng, Qiong Zhou, Wei Cheng, Ching Shang, Pei Han, Chiou-Hong Lin, Huei-Sheng Vincent Chen, Thomas Quertermous, Ching-Pin Chang
Genes encoding angiotensin-converting enzymes (Ace and Ace2) are essential for heart function regulation. Cardiac stress enhances Ace, but suppresses Ace2, expression in the heart, leading to a net production of angiotensin II that promotes cardiac hypertrophy and fibrosis. The regulatory mechanism that underlies the Ace2-to-Ace pathological switch, however, is unknown. Here we report that the Brahma-related gene-1 (Brg1) chromatin remodeler and forkhead box M1 (FoxM1) transcription factor cooperate within cardiac (coronary) endothelial cells of pathologically stressed hearts to trigger the Ace2-to-Ace enzyme switch, angiotensin I-to-II conversion, and cardiac hypertrophy...
September 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27593925/sensitization-of-retinoids-and-corticoids-to-epigenetic-drugs-in-myc-activated-lung-cancers-by-antitumor-reprogramming
#15
O A Romero, S Verdura, M Torres-Diz, A Gomez, S Moran, E Condom, M Esteller, A Villanueva, M Sanchez-Cespedes
Components of the SWI/SNF chromatin remodeling complex, including BRG1 (also SMARCA4), are inactivated in cancer. Among other functions, SWI/SNF orchestrates the response to retinoid acid (RA) and glucocorticoids (GC) involving downregulation of MYC. The epigenetic drugs SAHA and azacytidine, as well as RA and GC, are currently being used to treat some malignancies but their therapeutic potential in lung cancer is not well established. Here we aimed to determine the possible therapeutic effects of azacytidine and SAHA (A/S) alone or in combination with GC plus RA (GC/RA) in lung cancers with either BRG1 inactivation or MYC amplification...
September 5, 2016: Oncogene
https://www.readbyqxmd.com/read/27588112/h4k5-histone-acetylation-of-brg1-is-associated-with-heroin-administration-rather-than-addiction
#16
Limin Xu, Qingxiao Hong, Xiaoying Chen, Xuting Xu, Huifen Liu, Wenhua Zhou, Shiwei Duan
Diacetylmorphine hydrochloride (heroin) addiction is a chronic relapsing brain disorder that is a heavy public health burden worldwide. Brm/SWI2-related gene-1 (BRG1) is a tumor suppressor gene that can influence embryogenesis and the development of the cerebellum. The current study aimed to investigate the effect of histone H4 lysine 5 (H4K5) modifications on the BRG1 gene in brain tissue of the ventral tegmental area (VTA) of heroin-addicted rats. A total of 21 male Sprague Dawley rats were raised in a standard manner and underwent heroin self-administration training...
September 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27562491/concurrent-arid1a-and-arid1b-inactivation-in-endometrial-and-ovarian-dedifferentiated-carcinomas
#17
Mackenzie Coatham, Xiaodong Li, Anthony N Karnezis, Lien N Hoang, Basile Tessier-Cloutier, Bo Meng, Robert A Soslow, C Blake Gilks, David G Huntsman, Colin J R Stewart, Lynne M Postovit, Martin Köbel, Cheng-Han Lee
Dedifferentiated carcinoma of the endometrium or the ovary is an aggressive epithelial malignancy that comprises an endometrioid carcinoma together with an undifferentiated carcinoma. We recently reported that inactivation of BRG1 or INI1, core subunits of the switch/sucrose non-fermenting (SWI/SNF) complex, was the likely molecular event underlying dedifferentiation in about half of dedifferentiated carcinomas. In this study, we performed a genomic screen that included other members of the SWI/SNF complex to better delineate the molecular basis in the remainder of these tumours...
August 26, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27546619/protein-arginine-methyltransferase-5-functions-as-an-epigenetic-activator-of-the-androgen-receptor-to-promote-prostate-cancer-cell-growth
#18
X Deng, G Shao, H-T Zhang, C Li, D Zhang, L Cheng, B D Elzey, R Pili, T L Ratliff, J Huang, C-D Hu
Protein arginine methyltransferase 5 (PRMT5) is an emerging epigenetic enzyme that mainly represses transcription of target genes via symmetric dimethylation of arginine residues on histones H4R3, H3R8 and H2AR3. Accumulating evidence suggests that PRMT5 may function as an oncogene to drive cancer cell growth by epigenetic inactivation of several tumor suppressors. Here, we provide evidence that PRMT5 promotes prostate cancer cell growth by epigenetically activating transcription of the androgen receptor (AR) in prostate cancer cells...
August 22, 2016: Oncogene
https://www.readbyqxmd.com/read/27510977/brg1-plays-an-essential-role-in-development-and-homeostasis-of-the-duodenum-through-regulation-of-notch-signaling
#19
Yutaka Takada, Akihisa Fukuda, Tsutomu Chiba, Hiroshi Seno
Brg1, a core subunit of the SWI/SNF chromatin remodeling complex, is essential for development and homeostasis of various organs. However, the functional role of Brg1 in intestinal development and homeostasis, and the underlying molecular mechanism, remain unknown. We found that deletion of Brg1 in the mouse intestine resulted in growth impairment and early death associated with abnormal crypt-villous formation, skewed differentiation into secretory lineage cells, markedly increased apoptosis, and stem cell loss in the duodenum...
October 1, 2016: Development
https://www.readbyqxmd.com/read/27490482/myc-activation-and-bcl2l11-silencing-by-a-tumour-virus-through-the-large-scale-reconfiguration-of-enhancer-promoter-hubs
#20
C David Wood, Hildegonda Veenstra, Sarika Khasnis, Andrea Gunnell, Helen M Webb, Claire Shannon-Lowe, Simon Andrews, Cameron S Osborne, Michelle J West
Lymphomagenesis in the presence of deregulated MYC requires suppression of MYC-driven apoptosis, often through downregulation of the pro-apoptotic BCL2L11 gene (Bim). Transcription factors (EBNAs) encoded by the lymphoma-associated Epstein-Barr virus (EBV) activate MYC and silence BCL2L11. We show that the EBNA2 transactivator activates multiple MYC enhancers and reconfigures the MYC locus to increase upstream and decrease downstream enhancer-promoter interactions. EBNA2 recruits the BRG1 ATPase of the SWI/SNF remodeller to MYC enhancers and BRG1 is required for enhancer-promoter interactions in EBV-infected cells...
2016: ELife
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