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Transcription factor

Xu Chen, Stefan Gustafsson, Thomas Whitington, Yan Borné, Erik Lorentzen, Jitong Sun, Peter Almgren, Jun Su, Robert Karlsson, Jie Song, Yi Lu, Yiqiang Zhan, Sara Hägg, Per Svensson, Karin E Smedby, Susan L Slager, Erik Ingelsson, Cecilia M Lindgren, Andrew P Morris, Olle Melander, Thomas Karlsson, Ulf de Faire, Kenneth Caidahl, Gunnar Engström, Lars Lind, Mikael C I Karlsson, Nancy L Pedersen, Johan Frostegård, Patrik K E Magnusson
Phosphorylcholine (PC) is an epitope on oxidized low-density lipoprotein (oxLDL), apoptotic cells and several pathogens like Streptococcus pneumoniae. Immunoglobulin M against PC (IgM anti-PC) has the ability to inhibit uptake of oxLDL by macrophages and increase clearance of apoptotic cells. From our genome-wide association studies (GWAS) in four European-ancestry cohorts, six SNPs in 11q24.1 were discovered (in 3002 individuals) and replicated (in 646 individuals) to be associated with serum level of IgM anti-PC (the leading SNP rs35923643-G, combined beta=0...
March 14, 2018: Human Molecular Genetics
Min Young Kim, Ji Sook Kim, Seung Han Son, Chang Su Lim, Hea Young Eum, Dae Hyun Ha, Mi Ae Park, Eun Jung Baek, Buom-Yong Ryu, Ho Chul Kang, Vladimir N Uversky, Chul Geun Kim
During hematopoiesis, red blood cells originate from the hematopoietic stem cell reservoir. Although the regulation of erythropoiesis and globin expression has been intensively investigated, the underlining mechanisms are not fully understood, including the interplay between transcription factors and epigenetic factors. Here, we uncover that the Mbd2-free NuRD chromatin remodeling complex potentiates erythroid differentiation of proerythroblasts via managing functions of the CP2c complexes. We found that both Mbd2 and Mbd3 expression is downregulated during differentiation of MEL cells in vitro and in normal erythropoiesis in mouse bone marrow, and Mbd2 downregulation is crucial for erythropoiesis...
March 14, 2018: Nucleic Acids Research
Jiang He, Yuzu Zhao, Erhu Zhao, Xianxing Wang, Zhen Dong, Yibiao Chen, Liqun Yang, Hongjuan Cui
Background: The cancer-testis specific gene Opa interacting protein 5 (OIP5) is a testis-specific gene that is reactivated in many human cancers, but its functions in glioblastoma remain unclear. Here, we assessed the significance of OIP5 in the tumorigenesis and metastasis of glioblastoma for the first time. Methods: An immunohistochemistry assay was performed to detect OIP5 expression changes in glioblastoma patients. Overall survival analysis was performed to evaluate the prognostic significance of OIP5...
March 14, 2018: Neuro-oncology
Benedikt Hacker, Christoph Schultheiß, Michael Döring, Ursula Kurzik-Dumke
This study provides first insights into the involvement of hNOT/ALG3, the human counterpart of the Drosophila NOT and yeast ALG3 gene, in various putative molecular networks. HNOT/ALG3 encodes two translated transcripts encoding precursor proteins differing in their N-terminus and showing 33% identity with the yeast asparagine-linked glycosylation 3 (ALG3) protein. Experimental evidence for the functional homology of the proteins of fly and man in the N-glycosylation has still to be provided. In this study, using the yeast two-hybrid technique we identify 17 molecular partners of hNOT-1/ALG3-1...
March 14, 2018: Human Molecular Genetics
Peng Liu, Teng-Fei Zhou, Bao-An Qiu, Ying-Xiang Yang, Yong-Jian Zhu, Yang An, Wen-Chao Zhao, Yin-Tao Wu, Peng-Fei Ma, Jing-Bo Li, Nian-Xin Xia
Cholangiocarcinoma (CCA) is one of the most common hepatic and biliary malignancies, accounting for about 3% of all gastrointestinal tumors. GATA5 is a transcription factor capable of suppressing the development of various human cancer types. Transcriptional inactivation and CpG island (CGI) methylation of GATA3 and GATA5, two members of the GATA family of transcription factors, have been observed in some human cancers. But whether high-density CGI methylation of GATA5 is associated with the clinical course of CCA patients has not been clarified...
March 13, 2018: Translational Oncology
Dong-Keon Lee, Ji-Hee Kim, Joohwan Kim, Seunghwan Choi, MinSik Park, Wonjin Park, Suji Kim, Kyu-Sun Lee, Taesam Kim, Jiwon Jung, Yoon Kyung Choi, Kwon-Soo Ha, Moo-Ho Won, Timothy R Billiar, Young-Guen Kwon, Young-Myeong Kim
Regulated in development and DNA damage responses (REDD)-1, an inhibitor of mammalian target of rapamycin (mTOR), is induced by various cell stressors, including LPS, a major player in the pathogenesis of endotoxemic shock. However, the pathologic role of REDD-1 in endotoxemia is largely unknown. We found that LPS increased REDD-1 expression, nuclear transcription factor-κB (NF-κB) activation, and inflammation and that these responses were suppressed by REDD-1 knockdown and in REDD-1+/- macrophages. REDD-1 overexpression stimulated NF-κB-dependent inflammation without additional LPS stimulation...
March 16, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Yun Bai, Chuan Liu, Lei Fu, Xiaoshan Gong, Ce Dou, Zhen Cao, Hongyu Quan, Jianmei Li, Fei Kang, Jingjin Dai, Chunrong Zhao, Shiwu Dong
Endochondral ossification is crucial for bone formation in both adult bone repair process and embryo long-bone development. In endochondral ossification, bone marrow-derived mesenchymal stem cells (BMSCs) first differentiate to chondrocyte, BMSC-derived chondrocyte then endure a hypertrophic process to generate new bone. Endochondral ossification-based bone repair is a promising strategy to cure massive bone defect, which is a major clinical issue in orthopedics. However, challenges still remain for this novel strategy...
March 16, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Sukyoung Choi, Soohan Jung, Kwang Suk Ko
Coffee roasting affects the taste, color, and aroma of coffee. The Maillard reaction, a major reaction during the roasting process, produces melanoidin, which affects the overall antioxidant capacity and anti-inflammatory effects of coffee. In this experiment, coffee roasting was divided into four degrees: Light, Medium, City, and French. To examine the in vivo antioxidant and anti-inflammatory effects of coffee extracts with different roasting degrees, we used 10-week-old male C57BL/6 mice. Mice were pre-treated with coffee extracts for 10 days by oral gavage (300 mg/Kg...
March 16, 2018: Nutrients
Camilla Björkegren, Laura Baranello
Although our knowledge of chromatin organization has advanced significantly in recent years, much about the relationships between different features of genome architecture is still unknown. Folding of mammalian genomes into spatial domains is thought to depend on architectural proteins, other DNA-binding proteins, and different forms of RNA. In addition, emerging evidence points towards the possibility that the three-dimensional organisation of the genome is controlled by DNA topology. In this scenario, cohesin, CCCTC-binding factor (CTCF), transcription, DNA supercoiling, and topoisomerases are integrated to dictate different layers of genome organization, and the contribution of all four to gene control is an important direction of future studies...
March 16, 2018: International Journal of Molecular Sciences
Martin A Bewley, Richard C Budd, Eilise Ryan, Joby Cole, Paul Collini, Jennifer Marshall, Umme Kolsum, Gussie Beech, Richard D Emes, Irina Tcherniaeva, Guy A M Berbers, Sarah R Walmsley, Gavin Donaldson, Jadwiga A Wedzicha, Iain Kilty, William Rumsey, Yolanda Sanchez, Christopher E Brightling, Louise E Donnelly, Peter J Barnes, Dave Singh, Moira K B Whyte, David H Dockrell
RATIONALE: Previous studies have identified defects in bacterial phagocytosis by alveolar macrophages (AM) in patients with chronic obstructive pulmonary disease (COPD) but the mechanisms and clinical consequences remain incompletely defined. OBJECTIVES: To examine the effect of COPD on AM phagocytic responses and identify the mechanisms, clinical consequences and potential for therapeutic manipulation of these defects. METHODS: We isolated alveolar macrophages (AM) and monocyte-derived macrophages (MDM) from a cohort of COPD patients and controls within the MRC COPD-MAP consortium and measured phagocytosis of bacteria in relation to opsonic conditions and clinical features...
March 16, 2018: American Journal of Respiratory and Critical Care Medicine
Evgenia N Nikolova, Robyn L Stanfield, Jane Dyson, Peter E Wright
Many eukaryotic transcription factors recognize the epigenetic marker 5-methylcytosine (mC) at CpG sites in DNA. Despite their structural diversity, methyl-CpG-binding proteins (MBPs) share a common mode of recognition of mC methyl groups that involves hydrophobic pockets and weak hydrogen bonds of the CH---O type. The zinc finger protein Kaiso possesses a remarkably high specificity for methylated over unmethylated CpG sites. A key contribution to this specificity is provided by glutamate 535 (E535), which is optimally positioned to form multiple interactions with mCpG, including direct CH---O hydrogen bonds...
March 16, 2018: Biochemistry
Yongpeng Yao, Shanshan Li, Jiaqian Cao, Weiwei Liu, Keqiang Fan, Wensheng Xiang, Keqian Yang, Deming Kong, Weishan Wang
Here, we demonstrate an easy-to-implement and general biosensing strategy by coupling the small-molecule recognition of the bacterial allosteric transcription factor (aTF) with isothermal strand displacement amplification (SDA) in vitro. Based on this strategy, we developed two biosensors for the detection of an antiseptic, p-hydroxybenzoic acid, and a disease marker, uric acid, using bacterial aTF HosA and HucR, respectively, highlighting the great potential of this strategy for the development of small-molecule biosensors...
March 16, 2018: Chemical Communications: Chem Comm
Aruna Vashishta, Lukasz P Slomnicki, Maciej Pietrzak, Scott C Smith, Murali Kolikonda, Shivani P Naik, Rosanna Parlato, Michal Hetman
Ribosome biogenesis, including the RNA polymerase 1 (Pol1)-mediated transcription of rRNA, is regulated by the pro-epileptogenic mTOR pathway. Therefore, hippocampal Pol1 activity was examined in mouse models of epilepsy including kainic acid- and pilocarpine-induced status epilepticus (SE) as well as a single seizure in response to pentylenetetrazole (PTZ). Elevated 47S pre-rRNA levels were present acutely after induction of SE suggesting activation of Pol1. Conversely, after a single seizure, 47S pre-rRNA was transiently downregulated with increased levels of unprocessed 18S rRNA precursors in the cornu Ammonis (CA) region...
March 15, 2018: Molecular Neurobiology
Fırat Kurt, Ertugrul Filiz
Iron (Fe) is an essential element for plant life. Its deficiency impedes growth and development and excessive iron can cause the toxic effect via the Fenton reaction. Thus, plants have developed various mechanisms to acquire, distribute and utilize Fe for the maintenance of their iron homeostasis at cellular and systemic levels. A basic helix-loop-helix (bHLH) transcription factor family plays essential roles in many regulatory and development processes in plants. In this study, we aimed to understand the roles of bHLH38, bHLH39, bHLH100 and bHLH101 genes for Fe homeostasis in Arabidopsis, tomato, rice, soybean and maize species by using bioinformatics approaches...
March 15, 2018: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
Sribalasubashini Muralimanoharan, Youn-Tae Kwak, Carole R Mendelson
Dysregulation of human trophoblast invasion and differentiation with placental hypoxia can result in preeclampsia, a hypertensive disorder of pregnancy. Herein, we characterized the role and regulation of miR-1246, which is markedly induced during human syncytiotrophoblast differentiation. miR-1246 is known to target GSK3β and AXIN2, inhibitors of WNT/β-catenin signaling, which is crucial for placental development, and is predicted to target JARID2, which promotes silencing of developmentally regulated genes...
March 13, 2018: Endocrinology
Olivier Turc, François Tardieu
Abortion of reproductive organs is a major limiting factor of yield under water deficit, but is also a trait selected for by evolutionary processes. Youngest reproductive organs must be prone to abortion so older organs can finish their development in case of limited resources. Water deficit increases natural abortion via two developmentally-driven processes, namely a signal from the first fertilized ovaries and a simultaneous arrest of the expansive growth of all ovaries at a precise stage. In maize (Zea mays) subjected to water deficits typically encountered in dryland agriculture, these developmental mechanisms account for 90 % of drought-associated abortion and are irreversible three days after silk emergence...
March 13, 2018: Journal of Experimental Botany
Zhiyi Qin, Peter Stoilov, Xuegong Zhang, Yi Xing
Alternative first exons diversify the transcriptomes of eukaryotes by producing variants of the 5' Untranslated Regions (5'UTRs) and N-terminal coding sequences. Accurate transcriptome-wide detection of alternative first exons typically requires specialized experimental approaches that are designed to identify the 5' ends of transcripts. We developed a computational pipeline SEASTAR that identifies first exons from RNA-seq data alone then quantifies and compares alternative first exon usage across multiple biological conditions...
March 13, 2018: Nucleic Acids Research
Peng Wang, San-Pin Wu, Kelsey E Brooks, Andrew M Kelleher, Jessica Milano-Foster, Francesco J DeMayo, Thomas E Spencer
Forkhead box A2 (FOXA2) is a pioneer transcription factor involved in organ development, function and cancer. In the uterus, FOXA2 is essential for pregnancy and expressed specifically in the glands of the endometrium loss of FOXA2 function occurs during development of endometrial cancer in humans. The present study describes the development of a mouse model for conditional expression of mouse FOXA2. Using a system consisting of a minigene located at the Rosa26 locus, a CAG-S-mFOXA2 allele was generated in embryonic stem cells and subsequently in mice; before activation, the minigene is silent due to a floxed stop cassette inserted between the promoter and the transgene...
March 13, 2018: Endocrinology
Te-Sha Tsai, Sonika Tyagi, Justin C St John
STUDY QUESTION: What are the molecular differences between mitochondrial DNA (mtDNA)-deficient and mtDNA-normal oocytes and how does mitochondrial supplementation alter these? SUMMARY ANSWER: Changes to DNA methylation in a 5' cytosine-phosphate-guanine 3' (CpG) island in the mtDNA-specific replication factor (DNA polymerase gamma (POLG)) of mtDNA-deficient oocytes mediates an increase in mtDNA copy number by the 2-cell stage that positively modulates the expression of nuclear genes, which affect cellular and metabolic processes, following autologous mitochondrial supplementation...
March 13, 2018: Human Reproduction
Robert John Aitken
This article is a personal perspective on male infertility, a condition that is not only extremely prevalent but also a major reason for couples to resort to assisted reproductive technology. The introduction of intra-cytoplasmic sperm injection (ICSI) as a form of facilitated fertilization had a revolutionary impact on our capacity to treat cases of male infertility associated with severely-compromised semen quality. However, the widespread use of this technique is also thought to pose risks in terms of the incidence of miscarriage, the health and wellbeing of the offspring and perpetuation of the infertile phenotype into future generations...
March 13, 2018: Molecular Human Reproduction
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