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Gene expression regulation

Yuanfei Zhou, Tingxing Song, Jie Peng, Zheng Zhou, Hongkui Wei, Rui Zhou, Siwen Jiang, Jian Peng
Sirtuin 1 (SIRT1) regulates adipocyte and osteoblast differentiation. However, the underlying mechanism should be investigated. This study revealed that SIRT1 acts as a crucial repressor of adipogenesis. RNA-interference-mediated SIRT1 knockdown or genetic ablation enhances adipogenic potential, whereas SIRT1 overexpression inhibits adipogenesis in mesenchymal stem cells (MSCs). SIRT1 also deacetylates the histones of sFRP1, sFRP2, and Dact1 promoters; inhibits the mRNA expression of sFRP1, sFRP2, and Dact1; activates Wnt signaling pathways; and suppresses adipogenesis...
October 20, 2016: Oncotarget
Hanaa Alkharobi, Aishah Alhodhodi, Yousef Hawsawi, Hasanain Alkafaji, Deirdre Devine, Reem El-Gendy, James Beattie
Human dental pulp cells (DPCs), which are known to contain a subset of stem cells capable of reforming a dentin and pulp-like complex upon in vivo transplantation, were isolated from third molars of three healthy donors and differentiated to a matrix mineralisation phenotype using by culture in dexamethasone and l-ascorbic acid. qRT-PCR analysis of insulin-like growth factor ( IGF) axis gene expression indicated that all genes, except insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein-1 ( IGFBP-1), were expressed in DPCs...
September 24, 2016: Stem Cell Research
Lara Ianov, Ashok Kumar, Thomas C Foster
The expression of estrogen receptor alpha (ERα) varies across brain regions and changes with age and according to the previous history of estradiol exposure. ERα is regulated by a number of mechanisms including the level of mRNA (Esr1) expression. For this study, we took advantage of regional differences in hippocampal ERα expression to investigate DNA ERα promoter methylation at CpG dinucleotide sites as a potential epigenetic mechanism for regulating gene expression. Young and aged female Fischer 344 rats were ovariectomized, and Esr1 expression and ERα promoter methylation were examined in hippocampal regions CA1 and CA3, either 3 or 14 weeks following surgery...
September 28, 2016: Neurobiology of Aging
Anna Hojka-Osinska, Lucyna Budzko, Agnieszka Zmienko, Agnieszka Rybarczyk, Patrick Maillard, Agata Budkowska, Marek Figlerowicz, Paulina Jackowiak
Hepatitis C virus (HCV) infection is one of the major causes of chronic liver diseases. Unfortunately, the mechanisms of HCV infection-induced liver injury and host-virus interactions are still not well recognized. To better understand these processes we determined the changes in the host gene expression that occur during HCV infection of Huh-7.5 cells. As a result, we identified genes that may contribute to the immune and metabolic cellular responses to infection. Pathway enrichment analysis indicated that HCV induced an increased expression of genes involved in mitogen-activated protein kinases signaling, adipocytokine signaling, cell cycle and nitrogen metabolism...
October 25, 2016: Acta Biochimica Polonica
Agata Swiatkowska, Paulina Zydowicz, Joanna Sroka, Jerzy Ciesiołka
The p53 tumour suppressor protein is one of the major factors responsible for cell cycle regulation and protection against cancer development. This is why it is often referred to as "the guardian of the genome". On the other hand, mutations in the p53 gene are connected with more than 50% of tumours of various types. The thirty-six years of extensive research on the p53 gene and its protein products have shown how sophisticated the p53-based cell system control is. An additional level of complexity of the p53 research is connected with at least twelve p53 isoforms which have been identified in the cell...
October 25, 2016: Acta Biochimica Polonica
Julia H Chariker, Donald M Miller, Eric C Rouchka
G-quadruplex structures (G4) are found throughout the human genome and are known to play a regulatory role in a variety of molecular processes. Structurally, they have many configurations and can form from one or more DNA strands. At the gene level, they regulate gene expression and protein synthesis. In this paper, chromosomal-level patterns of distribution are analyzed on the human genome to identify high-level distribution patterns potentially related to global functional processes. Here we show unique high density banding patterns on individual chromosomes that are highly correlated, appearing in a mirror pattern, across forward and reverse DNA strands...
2016: PloS One
Yanfen Li, Malavika K Adur, Athilakshmi Kannan, Juanmahel Davila, Yuechao Zhao, Romana A Nowak, Milan K Bagchi, Indrani C Bagchi, Quanxi Li
Endometriosis, defined as growth of the endometrial cells outside the uterus, is an inflammatory disorder that is associated with chronic pelvic pain and infertility in women of childbearing age. Although the estrogen-dependence of endometriosis is well known, the role of progesterone in development of this disease remains poorly understood. In this study, we developed a disease model in which endometriosis was induced in the peritoneal cavities of immunocompetent female mice, and maintained with exogenous estrogen...
2016: PloS One
Akimasa Someya, Takako Ikegami, Koji Sakamoto, Isao Nagaoka
Osteoarthritis (OA) is one of the major joint diseases, and the synovial inflammation is involved in the pathogenesis and progression of OA. Glucosamine (GlcN) is widely used as a dietary supplement for OA, and is expected to exert the antiinflammatory action in OA. However, the detailed mechanism for the antiinflammatory action of GlcN remains poorly understood. In this study, to elucidate the molecular mechanism involved in the GlcN-medicated regulation of synovial cell activation, we comprehensively analyzed the effect of GlcN on the gene expression using a human synovial cell line MH7A by DNA microarray...
2016: PloS One
Suli Huang, Ziquan Lv, Yi Guo, Lu Li, Yanwei Zhang, Li Zhou, Binyao Yang, Shuang Wu, Ying Zhang, Changhui Xie, Shanshan Li, Jinquan Cheng
Circulating microRNAs (miRNAs) are emerging as novel disease biomarkers. Using a miRNA microarray, we previously showed that the whole blood level of let-7e-5p was significantly higher in ischemic stroke patients than in control subjects. However, the association between let-7e-5p expression and the occurrence of ischemic stroke remains unknown. In this study, we validated the expression levels of let-7e-5p in two case-control populations using miRNA TaqMan assays and further investigated the potential targets of let-7e-5p...
2016: PloS One
Dennis Liang Fei, Hayley Motowski, Rakesh Chatrikhi, Sameer Prasad, Jovian Yu, Shaojian Gao, Clara L Kielkopf, Robert K Bradley, Harold Varmus
We have asked how the common S34F mutation in the splicing factor U2AF1 regulates alternative splicing in lung cancer, and why wild-type U2AF1 is retained in cancers with this mutation. A human lung epithelial cell line was genetically modified so that U2AF1S34F is expressed from one of the two endogenous U2AF1 loci. By altering levels of mutant or wild-type U2AF1 in this cell line and by analyzing published data on human lung adenocarcinomas, we show that S34F-associated changes in alternative splicing are proportional to the ratio of S34F:wild-type gene products and not to absolute levels of either the mutant or wild-type factor...
October 2016: PLoS Genetics
Yuchen Gao, Xin Xiong, Spencer Wong, Emeric J Charles, Wendell A Lim, Lei S Qi
The ability to dynamically manipulate the transcriptome is important for studying how gene networks direct cellular functions and how network perturbations cause disease. Nuclease-dead CRISPR-dCas9 transcriptional regulators, while offering an approach for controlling individual gene expression, remain incapable of dynamically coordinating complex transcriptional events. Here, we describe a flexible dCas9-based platform for chemical-inducible complex gene regulation. From a screen of chemical- and light-inducible dimerization systems, we identified two potent chemical inducers that mediate efficient gene activation and repression in mammalian cells...
October 24, 2016: Nature Methods
Anne Buttgereit, Iva Lelios, Xueyang Yu, Melissa Vrohlings, Natalie R Krakoski, Emmanuel L Gautier, Ryuichi Nishinakamura, Burkhard Becher, Melanie Greter
Microglia are the resident macrophages of the central nervous system (CNS). Gene expression profiling has identified Sall1, which encodes a transcriptional regulator, as a microglial signature gene. We found that Sall1 was expressed by microglia but not by other members of the mononuclear phagocyte system or by other CNS-resident cells. Using Sall1 for microglia-specific gene targeting, we found that the cytokine receptor CSF1R was involved in the maintenance of adult microglia and that the receptor for the cytokine TGF-β suppressed activation of microglia...
October 24, 2016: Nature Immunology
Zhilei Zhao, Seiichiro Jinde, Chihiro Kakiuchi, Kiyoto Kasai
Several recent gene expression studies on schizophrenia, including one using monozygotic twins discordant for the disease, have reported the upregulation of adrenomedullin (ADM), which was initially identified as a vasodilator hormone. It has been hypothesized that upregulation of ADM may be a susceptibility factor for schizophrenia, although the exact role of ADM in the central nervous system remains unclear. In this study, we used a microarray analysis to investigate the changes in global gene expression induced by the administration of exogenous ADM in SK-N-SH cells, which allowed us to evaluate the effects of elevated ADM on the central nervous system...
October 21, 2016: Neuroreport
Hideki Ushiku, Keishi Yamashita, Hiroshi Kawamata, Mina Waraya, Hiroshi Katoh, Keigo Yokoi, Toshimichi Tanaka, Satoru Ishii, Nobuyuki Nishizawa, Mariko Kikuchi, Naoko Minatani, Ken Kojo, Hiroshi Tajima, Ryo Nishiyama, Takashi Kaizu, Yusuke Kumamoto, Masahiko Watanabe
OBJECTIVES: We have identified homeobox-only protein (HOPX) as a tumor suppressor gene in various human cancer, and its expression was reduced by promoter DNA hypermethylation. Homeobox-only protein is strongly expressed on pancreatic islet cells; however, clinical relevance of HOPX expression has remained elusive in pancreatic neuroendocrine tumor (pNET). METHODS: We investigated 36 patients with pNET who undertook surgical resection between 1988 and 2012 for HOPX expression and DNA methylation to reveal its clinical significance...
October 2016: Pancreas
Kaixuan Ren, Haitao Cui, Qinghua Xu, Chaoliang He, Gao Li, Xuesi Chen
Bone marrow-derived mesenchymal stem cells (BMSCs) possess vast potential for tissue engineering and regenerative medicine. In this study, an injectable hydrogel comprising poly(L-glutamic acid)-graft-tyramine (PLG-g-TA) with tunable microenvironment was developed via enzyme-catalyzed crosslinking, and used as artificial extracellular matrix (ECM) to explore the behaviors of BMSCs during three dimensional (3D) culture. It was found that the mechanical property, porous structure as well as degradation process of the hydrogels could be tuned by changing the copolymer concentration...
October 24, 2016: Biomacromolecules
Nicolas Unsain, Genevieve Dorval, JaeHyung Sheen, Philip A Barker
The Neurotrophin receptor associated death domain gene (Nradd/Nrh2/Plaidd) is a type I transmembrane protein with a unique and short N-terminal extracellular domain and a transmembrane and intracellular domain that bears high similarity to the p75 neurotrophin receptor (p75NTR/Ngfr). Initial studies suggested that NRADD regulates neurotrophin signaling but very little is known about its physiological roles. We have generated and characterized NRADD conditional and germ-line null mouse lines. These mice are viable and fertile and dońt show evident abnormalities...
October 24, 2016: Genesis: the Journal of Genetics and Development
Cheng-Gang Ou, Ji-Hua Mao, Li-Jie Liu, Cheng-Jiang Li, Huai-Fu Ren, Zhi-Wei Zhao, Fei-Yun Zhuang
Carrot is generally regarded as a biennial plant with an obligatory vernalization requirement. Early spring cultivation makes carrot plants vulnerable to premature bolting, which results in a loss of commercial value. However, our knowledge of flowering time genes and flowering mechanisms in carrot remain limited. We therefore performed transcriptome analysis to identify the major genes that regulate flowering time in carrot. The bolting behavior of carrot is influenced by low temperature, illumination intensity and photoperiod...
October 24, 2016: Plant Biology
Michael S Samuel, Nicola Rath, Siti F Masre, Sarah T Boyle, David A Greenhalgh, Marina Kochetkova, Sheila Bryson, David Stevenson, Michael F Olson
The serine/threonine kinases ROCK1 and ROCK2 are central mediators of actomyosin contractile force generation that act downstream of the RhoA small GTP-binding protein. As a result, they have key roles in regulating cell morphology and proliferation, and have been implicated in numerous pathological conditions and diseases including hypertension and cancer. Here we describe the generation of a gene-targeted mouse line that enables CRE-inducible expression of a conditionally-active fusion between the ROCK2 kinase domain and the hormone-binding domain of a mutated estrogen receptor (ROCK2:ER)...
October 24, 2016: Genesis: the Journal of Genetics and Development
D F Paulo, A M L Azeredo-Espin, L E C Canesin, R Vicentini, A C M Junqueira
MicroRNAs (miRNAs) are small noncoding RNAs that modulate gene expression through post-transcriptional regulation. Here, we report the identification and characterization of miRNAs in two closely related screwworm flies with different feeding habits: Cochliomyia hominivorax and Cochliomyia macellaria. The New World screwworm, C. hominivorax, is an obligatory parasite of warm-blooded vertebrates, whereas the secondary screwworm, C. macellaria, is a free-living organism that feeds on decaying organic matter. Here, the small RNA transcriptomes of adults and third-instar larvae of both species were sequenced...
October 24, 2016: Insect Molecular Biology
Pavel Sumazin, Yidong Chen, Lisa R Treviño, Stephen F Sarabia, Oliver A Hampton, Kayuri Patel, Toni-Ann Mistretta, Barry Zorman, Patrick Thompson, Andras Heczey, Sarah Comerford, David A Wheeler, Murali Chintagumpala, Rebecka Meyers, Dinesh Rakheja, Milton J Finegold, Gail Tomlinson, D Williams Parsons, Dolores López-Terrada
Despite being the most common liver cancer in children, hepatoblastoma (HB) is a rare neoplasm. Consequently, few pre-treatment tumors have been molecularly profiled and there are no validated prognostic or therapeutic biomarkers for HB patients. We report on the first large-scale effort to profile pre-treatment HBs at diagnosis. Our analysis of 88 clinically-annotated HBs revealed three risk-stratifying molecular subtypes that are characterized by differential activation of hepatic progenitor cell markers and metabolic pathways: high-risk tumors were characterized by up-regulated NFE2L2 activity, high LIN28B, HMGA2, SALL4 and AFP expression, and high coordinated expression of oncofetal proteins and stem cell markers; while low-risk tumors had low LIN28B and let-7 expression, and high HNF1A activity...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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