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https://www.readbyqxmd.com/read/29786685/regulation-of-chromatin-states-and-gene-expression-during-hsn-neuronal-maturation-is-mediated-by-eor-1-plzf-mau-2-cohesin-loader-and-swi-snf-complex
#1
Yoichi Shinkai, Masahiro Kuramochi, Motomichi Doi
Newborn neurons mature by distinct and sequential steps through the timely induction of specific gene expression programs in concert with epigenetic changes. However, it has been difficult to investigate the relationship between gene expression and epigenetic changes at a single-cell resolution during neuronal maturation. In this study, we investigated the maturation of hermaphrodite-specific neurons (HSNs) in C. elegans, which provided the link between chromatin dynamics, gene expression, and the degree of neuronal maturation at a single-cell resolution...
May 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29785027/targeting-g-quadruplex-dna-as-cognitive-function-therapy-for-atr-x-syndrome
#2
Norifumi Shioda, Yasushi Yabuki, Kouya Yamaguchi, Misaki Onozato, Yue Li, Kenji Kurosawa, Hideyuki Tanabe, Nobuhiko Okamoto, Takumi Era, Hiroshi Sugiyama, Takahito Wada, Kohji Fukunaga
Alpha-thalassemia X-linked intellectual disability (ATR-X) syndrome is caused by mutations in ATRX, which encodes a chromatin-remodeling protein. Genome-wide analyses in mouse and human cells indicate that ATRX tends to bind to G-rich sequences with a high potential to form G-quadruplexes. Here, we report that Atrx mutation induces aberrant upregulation of Xlr3b expression in the mouse brain, an outcome associated with neuronal pathogenesis displayed by ATR-X model mice. We show that ATRX normally binds to G-quadruplexes in CpG islands of the imprinted Xlr3b gene, regulating its expression by recruiting DNA methyltransferases...
May 21, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29783122/bix-01294-promotes-the-differentiation-of-adipose-mesenchymal-stem-cells-into-adipocytes-and-neural-cells-in-arbas-cashmere-goats
#3
Qing Wang, Xiao Wang, Defang Lai, Jin Deng, Zhuang Hou, Hao Liang, Dongjun Liu
Chromatin remodeling plays an essential role in regulating gene transcription. BIX-01294 is a specific inhibitor of histone methyltransferase G9a, which is responsible for methylation of histone H3 lysine 9 (H3K9) that can also regulate DNA methylation and chromatin remodeling. The purpose of this study was to investigate the effects of BIX-01294 on the potential of goat adipose derived stem cells (gADSCs) to differentiate into adipocytes and neural cells. To accomplish this, BIX-01294 was used to treat gADSCs for 24 h, and the global level of DNA methylation as well as the expression of genes related to cell proliferation, apoptosis and pluripotency were detected...
May 14, 2018: Research in Veterinary Science
https://www.readbyqxmd.com/read/29781253/developmental-plasticity-in-reptiles-insights-from-temperature-dependent-gene-expression-in-wall-lizard-embryos
#4
Nathalie Feiner, Alfredo Rago, Geoffrey M While, Tobias Uller
Many features of the development of reptiles are affected by temperature, but very little is known about how incubation temperature affects gene expression. Here, we provide a detailed case study of gene expression profiles in common wall lizard (Podarcis muralis) embryos developing at stressfully low (15°C) versus benign (24°C) temperature. For maximum comparability between the two temperature regimes, we selected a precise developmental stage early in embryogenesis defined by the number of somites. We used a split-clutch design and lizards from four different populations to evaluate the robustness of temperature-responsive gene expression profiles...
May 20, 2018: Journal of Experimental Zoology. Part A, Ecological and Integrative Physiology
https://www.readbyqxmd.com/read/29781103/targeting-ubiquitin-specific-protease-7-in-cancer-a-deubiquitinase-with-great-prospects
#5
REVIEW
Farjana Yeasmin Khusbu, Fang-Zhi Chen, Han-Chun Chen
Deubiquitinase (DUB)-mediated cleavage of ubiquitin chain balances ubiquitination and deubiquitination for determining protein fate. USP7 is one of the best characterized DUBs and functionally important. Numerous proteins have been identified as potential substrates and binding partners of USP7; those play crucial roles in diverse array of cellular and biological processes including tumour suppression, cell cycle, DNA repair, chromatin remodelling, and epigenetic regulation. This review aims at summarizing the current knowledge of this wide association of USP7 with many cellular processes that enlightens the possibility of abnormal USP7 activity in promoting oncogenesis and the importance of identification of specific inhibitors...
May 20, 2018: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/29779941/the-epigenetic-state-of-prdm16-regulated-enhancers-in-radial-glia-controls-cortical-neuron-position
#6
José-Manuel Baizabal, Meeta Mistry, Miguel Turrero García, Nicolás Gómez, Olubusola Olukoya, Diana Tran, Matthew B Johnson, Christopher A Walsh, Corey C Harwell
The epigenetic landscape is dynamically remodeled during neurogenesis. However, it is not understood how chromatin modifications in neural stem cells instruct the formation of complex structures in the brain. We report that the histone methyltransferase PRDM16 is required in radial glia to regulate lineage-autonomous and stage-specific gene expression programs that control number and position of upper layer cortical projection neurons. PRDM16 regulates the epigenetic state of transcriptional enhancers to activate genes involved in intermediate progenitor cell production and repress genes involved in cell migration...
May 15, 2018: Neuron
https://www.readbyqxmd.com/read/29779098/stability-of-chromatin-remodeling-complex-subunits-is-determined-by-their-phosphorylation-status
#7
A M Azieva, A A Sheinov, F A Galkin, S G Georgieva, N V Soshnikova
It was found that, in the differentiated cells of mouse brain, the level of core (Brg1 and BAF155) and specific (BRD7, BAF180, and PHF10) subunits of the chromatin-remodeling complex PBAF is reduced compared to the undifferentiated proliferating cells. Phosphorylation of PBAF complex subunits is required for maintaining their stability in differentiated brain cells.
March 2018: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29778661/epigenetic-dysregulation-of-zeb1-is-involved-in-lmo2-promoted-t-cell-acute-lymphoblastic-leukaemia-leukaemogenesis
#8
Chao Wu, Jianjun Li, Chenchen Tian, Wen Shi, Huimin Jiang, Zhen Zhang, Hang Wang, Quansheng Zhang, Wei Sun, Peiqing Sun, Rong Xiang, Shuang Yang
T-cell acute lymphoblastic leukaemia (T-ALL) is a hematological malignancy caused by the accumulation of genomic lesions that affect the development of T-cells. ZEB1, a member of zinc finger-homeodomain family transcription factor, exhibits crucial function in promoting T-cell differentiation and potentially acts as a tumor suppressor in T-ALL. However, the molecular mechanism by which ZEB1 regulates T-ALL leukaemogenesis remains obscure. Here, we showed that oncogenic LIM only 2 (LMO2) could recruit Sap18 and HDAC1 to assemble an epigenetic regulatory complex, thus inducing histone deacetylation in ZEB1 promoter and chromatin remodeling to achieve transcriptional repression...
May 17, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29776334/swi-snf-regulates-half-of-its-targets-without-the-need-of-atp-driven-nucleosome-remodeling-by-brahma
#9
Antonio Jordán-Pla, Simei Yu, Johan Waldholm, Thomas Källman, Ann-Kristin Östlund Farrants, Neus Visa
BACKGROUND: Brahma (BRM) is the only catalytic subunit of the SWI/SNF chromatin-remodeling complex of Drosophila melanogaster. The function of SWI/SNF in transcription has long been attributed to its ability to remodel nucleosomes, which requires the ATPase activity of BRM. However, recent studies have provided evidence for a non-catalytic function of BRM in the transcriptional regulation of a few specific genes. RESULTS: Here we have used RNA-seq and ChIP-seq to identify the BRM target genes in S2 cells, and we have used a catalytically inactive BRM mutant (K804R) that is unable to hydrolyze ATP to investigate the magnitude of the non-catalytic function of BRM in transcription regulation...
May 18, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29776169/effects-of-nucleosome-stability-on-remodeler-catalyzed-repositioning
#10
Aaron M Morgan, Sarah E LeGresley, Koan Briggs, Gada Al-Ani, Christopher J Fischer
Chromatin remodelers are molecular motors that play essential roles in the regulation of nucleosome positioning and chromatin accessibility. These machines couple the energy obtained from the binding and hydrolysis of ATP to the mechanical work of manipulating chromatin structure through processes that are not completely understood. Here we present a quantitative analysis of nucleosome repositioning by the imitation switch (ISWI) chromatin remodeler and demonstrate that nucleosome stability significantly impacts the observed activity...
March 2018: Physical Review. E
https://www.readbyqxmd.com/read/29774630/the-emerging-roles-of-long-non-coding-rna-in-cancer
#11
Anna Sanchez Calle, Yumi Kawamura, Yusuke Yamamoto, Fumitaka Takeshita, Takahiro Ochiya
Since comprehensive analysis of the mammalian genome has revealed that the vast majority of genomic products are transcribed in long non-coding RNAs (lncRNAs), increasing attention has been paid towards these transcripts. The applied next-generation sequencing technologies have provided accumulating evidence of dysregulated lncRNAs in cancer. The implication of this finding may be seen in many forms and at multiple levels. With impacts ranging from integrating chromatin remodeling complexes to regulating transcription and post-transcriptional processes, aberrant expression of lncRNAs may have repercussions in cell proliferation, tumor progression or metastasis...
May 17, 2018: Cancer Science
https://www.readbyqxmd.com/read/29774376/roles-of-heat-shock-factor-1-beyond-the-heat-shock-response
#12
REVIEW
János Barna, Péter Csermely, Tibor Vellai
Various stress factors leading to protein damage induce the activation of an evolutionarily conserved cell protective mechanism, the heat shock response (HSR), to maintain protein homeostasis in virtually all eukaryotic cells. Heat shock factor 1 (HSF1) plays a central role in the HSR. HSF1 was initially known as a transcription factor that upregulates genes encoding heat shock proteins (HSPs), also called molecular chaperones, which assist in refolding or degrading injured intracellular proteins. However, recent accumulating evidence indicates multiple additional functions for HSF1 beyond the activation of HSPs...
May 17, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29773426/stem-cell-transcription-factor-sox2-in-synovial-sarcoma-and-other-soft-tissue-tumors
#13
Heba Zayed, Iver Petersen
BACKGROUND: SOX2 has gained considerable interest as a pluripotency inducing gene. Co-transfection of SOX2 together with NANOG, KLF4 and c-MYC into adult fibroblasts was able to generate pluripotent stem cells. SOX2 has been reported to be expressed in synovial sarcoma, a tumor being characterized by the SS18-SSX gene fusion forming part of the SWI/SNF chromatin remodeling complex that affects histone methylation. The role of SOX2 in this tumor type as well as other soft tissue tumor entities however is still poorly characterized...
May 4, 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29772792/metabolic-regulation-of-hypoxia-inducible-transcription-factors-the-role-of-small-molecule-metabolites-and-iron
#14
REVIEW
Peter S J Bailey, James A Nathan
Hypoxia-inducible transcription factors (HIFs) facilitate cellular adaptations to low-oxygen environments. However, it is increasingly recognised that HIFs may be activated in response to metabolic stimuli, even when oxygen is present. Understanding the mechanisms for the crosstalk that exists between HIF signalling and metabolic pathways is therefore important. This review focuses on the metabolic regulation of HIFs by small molecule metabolites and iron, highlighting the latest studies that explore how tricarboxylic acid (TCA) cycle intermediates, 2-hydroxyglutarate (2-HG) and intracellular iron levels influence the HIF response through modulating the activity of prolyl hydroxylases (PHDs)...
May 17, 2018: Biomedicines
https://www.readbyqxmd.com/read/29771637/quantitative-imaging-of-chromatin-decompaction-in-living-cells
#15
Elisa Dultz, Roberta Mancini, Guido Polles, Pascal Vallotton, Frank Alber, Karsten Weis
Chromatin organization is highly dynamic and regulates transcription. Upon transcriptional activation, chromatin is remodeled and referred to as "open", but quantitative and dynamic data of this decompaction process are lacking. Here, we have developed a quantitative high-resolution microscopy assay in living yeast cells to visualize and quantify chromatin dynamics using the GAL7-10-1 locus as a model system. Upon transcriptional activation of these three clustered genes, we detect an increase of the mean distance across this locus by >100 nm...
May 17, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29769717/swi2-snf2-atpase-chr2-remodels-pri-mirnas-via-serrate-to-impede-mirna-production
#16
Zhiye Wang, Zeyang Ma, Claudia Castillo-González, Di Sun, Yanjun Li, Bin Yu, Baoyu Zhao, Pingwei Li, Xiuren Zhang
Chromatin remodelling factors (CHRs) typically function to alter chromatin structure. CHRs also reside in ribonucleoprotein complexes, but little is known about their RNA-related functions. Here we show that CHR2 (also known as BRM), the ATPase subunit of the large switch/sucrose non-fermentable (SWI/SNF) complex, is a partner of the Microprocessor component Serrate (SE). CHR2 promotes the transcription of primary microRNA precursors (pri-miRNAs) while repressing miRNA accumulation in vivo. Direct interaction with SE is required for post-transcriptional inhibition of miRNA accumulation by CHR2 but not for its transcriptional activity...
May 16, 2018: Nature
https://www.readbyqxmd.com/read/29768199/the-autism-related-protein-chd8-cooperates-with-c-ebp%C3%AE-to-regulate-adipogenesis
#17
Yasuyuki Kita, Yuta Katayama, Taichi Shiraishi, Takeru Oka, Tetsuya Sato, Mikita Suyama, Yasuyuki Ohkawa, Keishi Miyata, Yuichi Oike, Michiko Shirane, Masaaki Nishiyama, Keiichi I Nakayama
The gene encoding the chromatin remodeler CHD8 is the most frequently mutated gene in individuals with autism spectrum disorder (ASD). Heterozygous mutations in CHD8 give rise to ASD that is often accompanied by macrocephaly, gastrointestinal complaints, and slender habitus. Whereas most phenotypes of CHD8 haploinsufficiency likely result from delayed neurodevelopment, the mechanism underlying slender habitus has remained unknown. Here, we show that CHD8 interacts with CCAAT/enhancer-binding protein β (C/EBPβ) and promotes its transactivation activity during adipocyte differentiation...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29767721/bhd-associated-kidney-cancer-exhibits-unique-molecular-characteristics-and-a-wide-variety-of-variants-in-chromatin-remodeling-genes
#18
Hisashi Hasumi, Mitsuko Furuya, Kenji Tatsuno, Shogo Yamamoto, Masaya Baba, Yukiko Hasumi, Yasuhiro Isono, Kae Suzuki, Ryosuke Jikuya, Shinji Otake, Kentaro Muraoka, Kimito Osaka, Narihiko Hayashi, Kazuhide Makiyama, Yasuhide Miyoshi, Keiichi Kondo, Noboru Nakaigawa, Takashi Kawahara, Koji Izumi, Junichi Teranishi, Yasushi Yumura, Hiroji Uemura, Yoji Nagashima, Adam R Metwalli, Laura S Schmidt, Hiroyuki Aburatani, W Marston Linehan, Masahiro Yao
Birt-Hogg-Dubé (BHD) syndrome is a hereditary kidney cancer syndrome, which predisposes patients to develop kidney cancer, cutaneous fibrofolliculomas and pulmonary cysts. The responsible gene FLCN is a tumor suppressor for kidney cancer which plays an important role in energy homeostasis through the regulation of mitochondrial oxidative metabolism. However, the process by which FLCN-deficiency leads to renal tumorigenesis is unclear. In order to clarify molecular pathogenesis of BHD-associated kidney cancer, we conducted whole-exome sequencing analysis using next-generation sequencing technology as well as metabolite analysis using LC/MS and GC/MS...
May 14, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29767248/combined-treatment-with-pi3k-inhibitor-bkm120-and-parp-inhibitor-olaparib-is-effective-in-inhibiting-the-gastric-cancer-cells-with-arid1a-deficiency
#19
Lin Yang, Guanghai Yang, Yingjun Ding, Yu Huang, Shunfang Liu, Lei Zhou, Wenjie Wei, Jing Wang, Guangyuan Hu
Dual blockade of phosphoinositide 3-kinase (PI3K) and poly(ADP-ribose) polymerase (PARP) has been revealed to be an effective treatment strategy for breast, ovarian and prostate cancer. However, the efficacy of this combination for the treatment of gastric cancer, and potential predictive therapeutic biomarkers remain unclear. Recent evidence suggests that the deficiency of AT-rich interactive domain containing protein 1A (ARID1A), which is a crucial chromatin remodeling gene, sensitizes tumor cells to PI3K and PARP inhibitors...
May 16, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29765770/persistent-6-oh-bde-47-exposure-impairs-functional-neuronal-maturation-and-alters-expression-of-neurodevelopmentally-relevant-chromatin-remodelers
#20
Robert G Poston, Carissa J Dunn, Pushpita Sarkar, Ramendra N Saha
Polybrominated diphenyl ethers (PBDEs) are a pervasive class of brominated flame retardants that are present in the environment at particularly high levels, especially in the United States. Their environmental stability, propensity for bioaccumulation, and known potential for neurotoxicity has evoked interest regarding their effects on the developing nervous system. Exposure to PBDEs has been strongly associated with neurodevelopmental disorders. However, the details of their mechanistic roles in such disorders are incompletely understood...
January 2018: Environmental Epigenetics
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