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Enhancer transcription

Yoseb Song, Jongoh Shin, Yujin Jeong, Sangrak Jin, Jung-Kul Lee, Dong Rip Kim, Sun Chang Kim, Suhyung Cho, Byung-Kwan Cho
Autotrophic conversion of CO2 to value-added biochemicals has received considerable attention as a sustainable route to replace fossil fuels. Particularly, anaerobic acetogenic bacteria are naturally capable of reducing CO2 or CO to various metabolites. To fully utilize their biosynthetic potential, an understanding of acetogenesis-related genes and their regulatory elements is required. Here, we completed the genome sequence of the syngas fermenting Eubacterium limosum ATCC 8486 and determined its transcription start sites (TSS)...
October 20, 2017: Scientific Reports
Giuliana Rossi, Chiara Bonfanti, Stefania Antonini, Mattia Bastoni, Stefania Monteverde, Anna Innocenzi, Marielle Saclier, Valentina Taglietti, Graziella Messina
Muscular dystrophies are severe disorders due to mutations in structural genes, and are characterized by skeletal muscle wasting, compromised patient mobility, and respiratory functions. Although previous works suggested enhancing regeneration and muscle mass as therapeutic strategies, these led to no long-term benefits in humans. Mice lacking the transcription factor Nfix have delayed regeneration and a shift toward an oxidative fiber type. Here, we show that ablating or silencing the transcription factor Nfix ameliorates pathology in several forms of muscular dystrophy...
October 20, 2017: Nature Communications
Rongman Xu, Xiangdong Zhao, Yuanyuan Zhao, Bin Chen, Li Sun, Changgen Xu, Bo Shen, Mei Wang, Wenrong Xu, Wei Zhu
OBJECTIVES: Gastric cancer mesenchymal stem cells (GC-MSCs) can promote the development of tumour growth. The tumour-promoting role of tumour-associated MSCs and T cells has been demonstrated. T cells as the major immune cells may influence and induce a pro-tumour phenotype in MSCs. This study focused on whether CD4(+) T cells can affect GC-MSCs to promote gastric cancer growth. MATERIALS AND METHODS: CD4(+) T cells upregulation of programmed death ligand 1 (PD-L1) expression in GC-MSCs through the phosphorylated signal transducer and activator of transcription (p-STAT3) signalling pathway was confirmed by immunofluorescence, western blotting and RT-PCR...
October 22, 2017: Cell Proliferation
Alyssa Mitson-Salazar, Calman Prussin
There is an absolute requirement for Th2 cells in the pathogenesis of allergen-driven eosinophil-rich type 2 inflammation. Although Th2 cells are generally regarded as a homogeneous population, in the past decade there has been increasing evidence for a minority subpopulation of IL-5+ Th2 cells that have enhanced effector function. This IL-5+ Th2 subpopulation has been termed pathogenic effector Th2 (peTh2), as it exhibits greater effector function and disease association than conventional Th2 cells. peTh2 cells have a different expression profile, differentially express transcription factors, and preferentially use specific signaling pathways...
2017: Frontiers in Medicine
Giacomo Frattari, Lars Aagaard, Paul W Denton
The development of an effective HIV-1 eradication strategy relies upon a clear understanding of the cellular mechanisms involved in HIV-1 latency. Among such cellular processes, microRNA activities affect HIV-1 production by regulating viral transcripts as well as host cell HIV-1 dependency factors. miR-29a stands apart from other relevant microRNAs as a potential therapeutic target in HIV-1 eradication. In vitro experiments have shown that miR-29a binds to a sequence in the 3'UTR of viral transcripts and inhibits their expression...
October 1, 2017: Journal of Virus Eradication
Kilmer S McCully
Many pathogenic microorganisms have been demonstrated in atherosclerotic plaques and in cerebral plaques in dementia. Hyperhomocysteinemia, which is a risk factor for atherosclerosis and dementia, is caused by dysregulation of methionine metabolism secondary to deficiency of the allosteric regulator, adenosyl methionine. Deficiency of adenosyl methionine results from increased polyamine biosynthesis by infected host cells, causing increased activity of ornithine decarboxylase, decreased nitric oxide and peroxynitrate formation and impaired immune reactions...
2017: Frontiers in Aging Neuroscience
Chun-Chung Wang, Jui-Hung Yen, Yi-Cheng Cheng, Chia-Yu Lin, Cheng-Ta Hsieh, Rung-Jiun Gau, Shu-Jiau Chiou, Hwan-You Chang
Obesity, the excessive accumulation of lipids in the body, is closely associated with many prevalent human disorders. Continued efforts to identify plant extracts that exhibit anti-obesity effects have drawn much attention. This study investigated whether a Polygala tenuifolia extract (PTE) possesses anti-obesity activity and how PTE may affect liver gene expression and gut microbiota. We used 3T3-L1 adipocytes and a high-fat diet-induced obese mouse model to determine the effects of PTE on lipid accumulation...
2017: Food & Nutrition Research
Hui Li, Yanglin Ding, Yiting Shi, Xiaoyan Zhang, Shuqun Zhang, Zhizhong Gong, Shuhua Yang
Low temperatures affect plant growth, development, productivity, and ecological distribution. Expression of the C-repeat-binding factor (CBF) transcription factors is induced by cold stress, which in turn activates downstream cold-responsive (COR) genes that are required for the acquisition of freezing tolerance. Inducer of CBF expression 1 (ICE1) is a master regulator of CBFs, and ICE1 stability is crucial for its function. However, the regulation of ICE1 is not well understood. Here, we report that mitogen-activated protein kinase 3 (MPK3) and MPK6 interact with and phosphorylate ICE1, which reduces its stability and transcriptional activity...
October 12, 2017: Developmental Cell
Chunzhao Zhao, Pengcheng Wang, Tong Si, Chuan-Chih Hsu, Lu Wang, Omar Zayed, Zheping Yu, Yingfang Zhu, Juan Dong, W Andy Tao, Jian-Kang Zhu
Mitogen-activated protein kinase cascades are important signaling modules that convert environmental stimuli into cellular responses. We show that MPK3, MPK4, and MPK6 are rapidly activated after cold treatment. The mpk3 and mpk6 mutants display increased expression of CBF genes and enhanced freezing tolerance, whereas constitutive activation of the MKK4/5-MPK3/6 cascade in plants causes reduced expression of CBF genes and hypersensitivity to freezing, suggesting that the MKK4/5-MPK3/6 cascade negatively regulates the cold response...
October 12, 2017: Developmental Cell
Xiong Zheng, Juan Wang, Yinguang Chen, Yuanyuan Wei
Although the toxicity of silver nanoparticles (Ag NPs or nanosilver) to model bacteria has been reported, the effects of Ag NPs on microbial denitrification under anoxic conditions and the mechanism of Ag NPs induced-toxicity to denitrification remain unclear. In this study, the effects of Ag NPs on Paracoccus denitrificans under anoxic conditions were investigated, and the mechanism was explored by analyzing the transcriptional and proteomic responses of bacteria to Ag NPs. The presence of 5mg/L Ag NPs led to excessive nitrate accumulation (232...
October 16, 2017: Journal of Hazardous Materials
Guangyuan Wang, Delong Li, Zhengang Miao, Shanshan Zhang, Wenxing Liang, Lin Liu
Yarrowia lipolytica is considered as a promising microbial cell factory for bio-oil production due to its ability to accumulate a large amount of lipid. However, the regulation of lipid metabolism in this oleaginous yeast is elusive. In this study, the MHY1 gene was disrupted, and 43.1% (w/w) intracellular oil based on cell dry weight was obtained from the disruptant M-MHY1, while only 30.2% (w/w) lipid based on cell dry weight was obtained from the reference strain. RNA-seq was then performed to analyze transcriptional changes during lipid biosynthesis after MHY1 gene inactivation...
October 18, 2017: Biochimica et Biophysica Acta
Jun Arai, Kaku Goto, Anthony Stephanou, Yasushi Tanoue, Sayaka Ito, Ryosuke Muroyama, Yasuo Matsubara, Ryo Nakagawa, Sayuri Morimoto, Yoshimi Kaise, Lay Ahyoung Lim, Hitoshi Yoshida, Naoya Kato
BACKGROUND AND AIM: The multi-kinase inhibitor regorafenib (REG) was recently demonstrated to be effective in patients with sorafenib (SOR)-resistant hepatocellular carcinoma (HCC). Interestingly, SOR is known to enhance the accumulation of membrane-bound MHC class I polypeptide-related sequence A (mMICA) in HCC cells, and to block production of soluble MICA (sMICA), an immunological decoy. In addition, MICA is associated with HCC in patients with chronic hepatitis C. We have now compared the impact of REG and SOR on MICA in HCC cells, as well as the immunotherapeutic implications thereof...
October 21, 2017: Journal of Gastroenterology and Hepatology
Alison Taylor, David Rothstein, Christopher Rudd
The impact of PD-1 immune checkpoint therapy prompts exploration of other strategies to downregulate PD-1 for cancer therapy. We previously showed that the serine/threonine kinase, glycogen synthase kinase GSK-3α/β, is a central regulator of PD-1 transcription in CD8+ T cells. Here, we show that the use of small molecule inhibitors of GSK-3α/β (GSK-3i) to reduce pcdc1 (PD-1) transcription and expression was as effective as anti-PD-1 and PDL-1 blocking antibodies in the control of B16 melanoma, or EL4 lymphoma, in primary tumor and metastatic settings...
October 20, 2017: Cancer Research
Nina Judith Hos, Raja Ganesan, Saray Gutiérrez, Deniz Hos, Jennifer Klimek, Zeinab Abdullah, Martin Krönke, Nirmal Robinson
Salmonella enterica serovar Typhimurium exploits the host's type I interferon (IFN-I) response to induce receptor-interacting protein (RIP) kinase-mediated necroptosis in macrophages. However, the events that drive necroptosis execution downstream of IFN-I and RIP signaling remain elusive. In this study, we demonstrate that S Typhimurium infection causes IFN-I-mediated up-regulation of the mitochondrial phosphatase Pgam5 through RIP3. Pgam5 subsequently interacts with Nrf2, which sequesters Nrf2 in the cytosol, thereby repressing the transcription of Nrf2-dependent antioxidative genes...
October 20, 2017: Journal of Cell Biology
Maria Rusan, Kapsok Li, Yvonne Li, Camilla L Christensen, Brian J Abraham, Nicholas Kwiatkowski, Kevin A Buczkowski, Bruno Bockorny, Ting Chen, Shuai Li, Kevin Rhee, Haikuo Zhang, Wankun Chen, Hideki Terai, Tiffany Tavares, Alan L Leggett, Tianxia Li, Yichen Wang, Tinghu Zhang, Tae-Jung Kim, Sook-Hee Hong, Neermala Poudel-Neupane, Michael Silkes, Tenny Mudianto, Li Tan, Takeshi Shimamura, Matthew Meyerson, Adam J Bass, Hideo Watanabe, Nathanael S Gray, Richard A Young, Kwok-Kin Wong, Peter S Hammerman
Acquired drug resistance is a major factor limiting the effectiveness of targeted cancer therapies. Targeting tumors with kinase inhibitors induces complex adaptive programs that promote the persistence of a fraction of the original cell population, facilitating the eventual outgrowth of inhibitor-resistant tumor clones. We show that the addition of a newly identified CDK7/12 inhibitor, THZ1, to targeted therapy enhances cell killing and impedes the emergence of drug-resistant cell populations in diverse cellular and in vivo cancer models...
October 20, 2017: Cancer Discovery
Biao Wang, Zhen Tang, Huiyuan Gong, Li Zhu, Xuegang Liu
A recent study indicated that high Wnt5a expression is associated with poor prognosis in NSCLC patients, however, the underlying mechanism was not clear yet. Immunohistochemistry and Western blotting was performed to examine the protein expression level in NSCLC tissues and cell lines. The role of Wnt5a in clone formation, invasiveness, migration and epithelial-to-mesenchymal transition (EMT) of NSCLC cells were studied. Luciferase reporter assay was used to evaluate the Tcf/Lef transcriptional activity. For assessing the effects of Wnt5a on tumor growth and metastasis in vivo , A549 cells transfected with sh-Wnt5a were subcutaneously or orthotopically injected into nude mice...
October 20, 2017: Bioscience Reports
Jose L Medrano, Francisco J Naya
The distinct morphological and functional properties of the cardiac chambers arise from an elaborate developmental program involving cell lineage determination, morphogenesis, and dynamic spatiotemporal gene expression patterns. While a number of transcription factors have been identified for proper gene regulation in the chambers, the complete transcriptional network that controls these patterns remains poorly defined. Previous studies have implicated the MEF2C transcription factor in the regulation of chamber-restricted enhancers...
October 20, 2017: Journal of Biological Chemistry
Vera Carniello, Akshay K Harapanahalli, Henk J Busscher, Henny C van der Mei
Nisin-associated-sensitivity-response-regulator (NsaRS) in Staphylococcus aureus is important for its adhesion to surfaces and resistance against antibiotics, like nisin. NsaRS consists of an intra-membrane-located sensor NsaS and a cytoplasmatically-located response-regulator NsaR, which becomes activated upon receiving phosphate groups from the intra-membrane-located sensor. HYPOTHESIS: The intra-membrane location of the NsaS sensor leads us to hypothesize that the two-component NsaRS system not only senses "chemical" (nisin) but also "mechanical" (adhesion) stresses to modulate efflux of antibiotics from the cytoplasm...
October 7, 2017: Journal of Colloid and Interface Science
Boyan Bonev, Netta Mendelson Cohen, Quentin Szabo, Lauriane Fritsch, Giorgio L Papadopoulos, Yaniv Lubling, Xiaole Xu, Xiaodan Lv, Jean-Philippe Hugnot, Amos Tanay, Giacomo Cavalli
Chromosome conformation capture technologies have revealed important insights into genome folding. Yet, how spatial genome architecture is related to gene expression and cell fate remains unclear. We comprehensively mapped 3D chromatin organization during mouse neural differentiation in vitro and in vivo, generating the highest-resolution Hi-C maps available to date. We found that transcription is correlated with chromatin insulation and long-range interactions, but dCas9-mediated activation is insufficient for creating TAD boundaries de novo...
October 19, 2017: Cell
Marcela Rodrigues de Camargo, Carolina Mendonça Gorgulho, Cecília Pessoa Rodrigues, Marcimara Penitenti, Juliana Cristina Longo Frederico, Maria Aparecida Marchesan Rodrigues, Ramon Kaneno
AIM: Considering the central role of dendritic cells (DCs) on the development of an antitumor immune response, in this study we used a murine model to evaluate how DC transfection with drug-treated tumor cell RNA changes their phenotype, and whether transfection enhances the in vivo effectiveness of a DC-based antitumor vaccine. MATERIALS AND METHODS: MC-38 colorectal tumor cells were pretreated with the minimum effective concentration of 5-fluorouracil (5-FU), then their total RNA was extracted and transfected into DCs...
October 2017: Cancer Biotherapy & Radiopharmaceuticals
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