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Taketo Nishikawaji, Yoshimitsu Akiyama, Shu Shimada, Kazuyuki Kojima, Tatsuyuki Kawano, Yoshinobu Eishi, Yasuhito Yuasa, Shinji Tanaka
SETDB2 is a histone H3 lysine 9 (H3K9) tri-methyltransferase that is involved in transcriptional gene silencing. Since it is still unknown whether SETDB2 is linked to carcinogenesis, we studied alterations and functions of SETDB2 in human gastric cancers (GCs). SETDB2 protein was highly expressed in 30 of 72 (41.7%) primary GC tissues compared with their normal counterparts by immunohistochemistry. SETDB2 overexpression was significantly associated with the late stage of GCs (P<0.05) and poor prognosis of GC patients (P<0...
August 26, 2016: Oncotarget
Manuel Roqueta-Rivera, Ryan M Esquejo, Peter E Phelan, Katalin Sandor, Bence Daniel, Fabienne Foufelle, Jun Ding, Xiaoman Li, Sepideh Khorasanizadeh, Timothy F Osborne
Transcriptional and chromatin regulations mediate the liver response to nutrient availability. The role of chromatin factors involved in hormonal regulation in response to fasting is not fully understood. We have identified SETDB2, a glucocorticoid-induced putative epigenetic modifier, as a positive regulator of GR-mediated gene activation in liver. Insig2a increases during fasting to limit lipid synthesis, but the mechanism of induction is unknown. We show Insig2a induction is GR-SETDB2 dependent. SETDB2 facilitates GR chromatin enrichment and is key to glucocorticoid-dependent enhancer-promoter interactions...
September 13, 2016: Cell Metabolism
Amitabh Das, Sun Hwa Kim, Sarder Arifuzzaman, Taeho Yoon, Jin Choul Chai, Young Seek Lee, Kyoung Sun Park, Kyoung Hwa Jung, Young Gyu Chai
BACKGROUND: Microglia are resident myeloid cells in the CNS that are activated by infection, neuronal injury, and inflammation. Established BV2 microglial cell lines have been the primary in vitro models used to study neuroinflammation for more than a decade because they reduce the requirement of continuously maintaining cell preparations and animal experimentation models. However, doubt has recently been raised regarding the value of BV2 cell lines as a model system. METHODS: We used triplicate RNA sequencing (RNA-seq) to investigate the molecular signature of primary and BV2 microglial cell lines using two transcriptomic techniques: global transcriptomic biological triplicate RNA-seq and quantitative real-time PCR...
2016: Journal of Neuroinflammation
R J Holt, C Vandiedonck, S A Willis-Owen, J C Knight, W O Cookson, M F Moffatt, Y Zhang
No abstract text is available yet for this article.
May 12, 2016: Genes and Immunity
Ryo Maekawa, Lifa Lee, Maki Okada, Hiromi Asada, Masahiro Shinagawa, Isao Tamura, Shun Sato, Hiroshi Tamura, Norihiro Sugino
BACKGROUND: The ovulatory LH surge rapidly alters the expression of steroidogenesis-related genes such as steroidogenic acute regulatory protein (StAR) in granulosa cells (GCs) undergoing luteinization. We recently reported that histone modifications contribute to these changes. Histone modifications are regulated by a variety of histone modification enzymes. This study investigated the changes in gene expression of histone modification enzymes in rat GCs undergoing luteinization after the induction of ovulation...
2016: Journal of Ovarian Research
Danielle N Kroetz, Ronald M Allen, Matthew A Schaller, Cleyton Cavallaro, Toshihiro Ito, Steven L Kunkel
Influenza A virus (IAV) is an airborne pathogen that causes significant morbidity and mortality each year. Macrophages (Mϕ) are the first immune population to encounter IAV virions in the lungs and are required to control infection. In the present study, we explored the mechanism by which cytokine signaling regulates the phenotype and function of Mϕ via epigenetic modification of chromatin. We have found that type I interferon (IFN-I) potently upregulates the lysine methyltransferase Setdb2 in murine and human Mϕ, and in turn Setdb2 regulates Mϕ-mediated immunity in response to IAV...
December 2015: PLoS Pathogens
M A Abdalhag, T Zhang, Q C Fan, X Q Zhang, G X Zhang, J Y Wang, Y Wei, Y J Wang
Body weight is one of the most important economic traits in the poultry industry. In the present study, a custom SNP Beadchip was used to analyze the association between those 15 SNPs and 12 growth traits of Jinghai yellow chickens, and other important genetic parameters were also calculated and analyzed. The results indicated that nine of the 15 SNPs were associated with growth traits in Jinghai yellow chickens (P < 0.05), and the identified SNPs were also in linkage disequilibrium. Five of the nine identified SNPs were mainly associated with all of the growth traits, which indicated that those five SNPs might have significant influence on Jinghai yellow chicken growth traits...
2015: Genetics and Molecular Research: GMR
R J Holt, C Vandiedonck, S A Willis-Owen, J C Knight, W O Cookson, M F Moffatt, Y Zhang
The immunoglobulin E (IgE)-associated locus on human chromosome 13q14 influencing asthma-related traits contains the genes PHF11 and SETDB2. SETDB2 is located in the same linkage disequilibrium region as PHF11 and polymorphisms within SETDB2 have been shown to associate with total serum IgE levels. In this report, we sequenced the 15 exons of SETDB2 and identified a single previously ungenotyped mutation (AT/G, rs386770867) in the 5'-untranslated region of the gene. The polymorphism was found to be significantly associated with serum IgE levels in our asthma cohort (P=0...
October 2015: Genes and Immunity
Juliana T Maricato, Maria N Furtado, Maisa C Takenaka, Edsel R M Nunes, Patricia Fincatti, Fabiana M Meliso, Ismael D C G da Silva, Miriam G Jasiulionis, Maria Cecília de Araripe Sucupira, Ricardo Sobhie Diaz, Luiz M R Janini
Epigenetic modifications refer to a number of biological processes which alter the structure of chromatin and its transcriptional activity such as DNA methylation and histone post-translational processing. Studies have tried to elucidate how the viral genome and its products are affected by epigenetic modifications imposed by cell machinery and how it affects the ability of the virus to either, replicate and produce a viable progeny or be driven to latency. The purpose of this study was to evaluate epigenetic modifications in PBMCs and CD4+ cells after HIV-1 infection analyzing three approaches: (i) global DNA- methylation; (ii) qPCR array and (iii) western blot...
2015: PloS One
Lanxin Liu, Sarah Kimball, Hui Liu, Andreana Holowatyj, Zeng-Quan Yang
Histone lysine methyltransferases (HMTs), a large class of enzymes that catalyze site-specific methylation of lysine residues on histones and other proteins, play critical roles in controlling transcription, chromatin architecture, and cellular differentiation. However, the genomic landscape and clinical significance of HMTs in breast cancer remain poorly characterized. Here, we conducted a meta-analysis of approximately 50 HMTs in breast cancer and identified associations among recurrent copy number alterations, mutations, gene expression, and clinical outcome...
February 10, 2015: Oncotarget
Christopher Schliehe, Elizabeth K Flynn, Bojan Vilagos, Udochuku Richson, Savitha Swaminathan, Berislav Bosnjak, Lisa Bauer, Richard K Kandasamy, Isabel M Griesshammer, Lindsay Kosack, Frank Schmitz, Vladimir Litvak, James Sissons, Alexander Lercher, Anannya Bhattacharya, Kseniya Khamina, Anna L Trivett, Lino Tessarollo, Ildiko Mesteri, Anastasiya Hladik, Doron Merkler, Stefan Kubicek, Sylvia Knapp, Michelle M Epstein, David E Symer, Alan Aderem, Andreas Bergthaler
Immune responses are tightly regulated to ensure efficient pathogen clearance while avoiding tissue damage. Here we report that Setdb2 was the only protein lysine methyltransferase induced during infection with influenza virus. Setdb2 expression depended on signaling via type I interferons, and Setdb2 repressed expression of the gene encoding the neutrophil attractant CXCL1 and other genes that are targets of the transcription factor NF-κB. This coincided with occupancy by Setdb2 at the Cxcl1 promoter, which in the absence of Setdb2 displayed diminished trimethylation of histone H3 Lys9 (H3K9me3)...
January 2015: Nature Immunology
Youming Zhang, Charlotte Dean, Lauren Chessum, Dao Nguyen, Michelle Stewart, Martin Taylor, William O Cookson, Miriam F Moffatt
Previously, human genetic studies have shown association between polymorphisms within the gene encoding plant homeodomain zinc finger protein 11 (PHF11) and asthma-related phenotypes. Initial functional studies have suggested that PHF11 may be involved in the immune response through regulation of T cell activities. In order to study further the gene's functions, we have investigated the mouse Phf11 locus. We have established and characterised a mouse line harbouring a point mutation in the PHD domain of Phf11...
December 2014: Mammalian Genome: Official Journal of the International Mammalian Genome Society
Youn Jin Choi, Hye Rim Oh, Mi Ryoung Choi, Min Gwak, Chang Hyeok An, Yeun Jun Chung, Nam Jin Yoo, Sug Hyung Lee
Histone methyltransferase (HMT), which catalyzes a histone methylation, is frequently altered in cancers at mutation and expression levels. The aims of this study were to explore whether SETD1B, SETDB2, and SETD2, SET domain-containing HMT genes, are mutated and expressionally altered in gastric (GC) and colorectal cancers (CRC). In a public database, we found that SETD1B, SETDB2, and SETD2 had mononucleotide repeats in coding sequences that might be mutation targets in cancers with microsatellite instability (MSI)...
August 2014: Human Pathology
Ting-Ting Du, Peng-Fei Xu, Zhi-Wei Dong, Hong-Bo Fan, Yi Jin, Mei Dong, Yi Chen, Wei-Jun Pan, Rui-Bao Ren, Ting-Xi Liu, Min Deng, Qiu-Hua Huang
As the primary driving forces of gastrulation, convergence and extension (C&E) movements lead to a medio-lateral narrowing and an anterior-posterior elongation of the embryonic body axis. Histone methylation as a post-translational modification plays a critical role in early embryonic development, but its functions in C&E movements remain largely unknown. Here, we show that the setdb2-dvr1 transcriptional cascade plays a critical role in C&E movements during zebrafish gastrulation. Knockdown of Setdb2, a SET domain-containing protein possessing a potential histone H3K9 methyltransferase activity, induced abnormal C&E movements, resulting in anterior-posterior shortening and medio-lateral expansion of the embryonic axis, as well as abnormal notochord cell polarity...
August 15, 2014: Developmental Biology
Holly N Cukier, Joycelyn M Lee, Deqiong Ma, Juan I Young, Vera Mayo, Brittany L Butler, Sandhya S Ramsook, Joseph A Rantus, Alexander J Abrams, Patrice L Whitehead, Harry H Wright, Ruth K Abramson, Jonathan L Haines, Michael L Cuccaro, Margaret A Pericak-Vance, John R Gilbert
The methyl-CpG-binding domain (MBD) gene family was first linked to autism over a decade ago when Rett syndrome, which falls under the umbrella of autism spectrum disorders (ASDs), was revealed to be predominantly caused by MECP2 mutations. Since that time, MECP2 alterations have been recognized in idiopathic ASD patients by us and others. Individuals with deletions across the MBD5 gene also present with ASDs, impaired speech, intellectual difficulties, repetitive behaviors, and epilepsy. These findings suggest that further investigations of the MBD gene family may reveal additional associations related to autism...
December 2012: Autism Research: Official Journal of the International Society for Autism Research
H Parker, M J J Rose-Zerilli, A Parker, T Chaplin, R Wade, A Gardiner, M Griffiths, A Collins, B D Young, D G Oscier, J C Strefford
Historically, genes targeted by recurrent chromosomal deletions have been identified within the smallest genomic region shared in all patients, the minimally deleted region (MDR). However, deletions this small do not occur in all patients and are a simplification of the impact larger heterogeneous deletions have during carcinogenesis. We use the example of 13q14 deletions in chronic lymphocytic leukemia to show that genes outside MDRs are associated with disease progression. Genomic profiling of 224 patients identified 205 copy number alterations on chromosome 13 in 132 cases...
March 2011: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Cathryn A Hogarth, Debra Mitchell, Ryan Evanoff, Christopher Small, Michael Griswold
Meiosis is unique to germ cells and occurs in a sex-specific manner. The genes regulating meiotic initiation in either sex are yet to be fully elucidated. Recent studies have revealed the importance of retinoic acid and one of its target genes, Stra8, in meiotic initiation in both sexes. Microarray analysis of whole murine embryonic ovary and postnatal testis time course data revealed a single peak of Stra8 expression in each organ at the onset of meiosis; at Embryonic Day 14.5 in the ovary and 10 days postpartum in the testis...
January 2011: Biology of Reproduction
Claire Falandry, Geneviève Fourel, Vincent Galy, Tutik Ristriani, Béatrice Horard, Elsa Bensimon, Gilles Salles, Eric Gilson, Frédérique Magdinier
Proteins bearing a SET domain have been shown to methylate lysine residues in histones and contribute to chromatin architecture. Methylation of histone H3 at lysine 9 (H3K9) has emerged as an important player in the formation of heterochromatin, chromatin condensation, and transcriptional repression. Here, we have characterized a previously undescribed member of the histone H3K9 methyltransferase family named CLLD8 (or SETDB2 or KMT1F). This protein contributes to the trimethylation of both interspersed repetitive elements and centromere-associated repeats and participates in the recruitment of heterochromatin protein 1 to centromeres...
June 25, 2010: Journal of Biological Chemistry
Peng-Fei Xu, Kang-Yong Zhu, Yi Jin, Yi Chen, Xiao-Jian Sun, Min Deng, Sai-Juan Chen, Zhu Chen, Ting Xi Liu
Dorsal organizer formation is one of the most critical steps in early embryonic development. Several genes and signaling pathways that positively regulate the dorsal organizer development have been identified; however, little is known about the factor(s) that negatively regulates the organizer formation. Here, we show that Setdb2, a SET domain-containing protein possessing potential histone H3K9 methyltransferase activity, restricts dorsal organizer development and regulates left-right asymmetry by suppressing fibroblast growth factor 8 (fgf8) expression...
February 9, 2010: Proceedings of the National Academy of Sciences of the United States of America
Rachel Van Duyne, Rebecca Easley, Weilin Wu, Reem Berro, Caitlin Pedati, Zachary Klase, Kylene Kehn-Hall, Elizabeth K Flynn, David E Symer, Fatah Kashanchi
BACKGROUND: The rate of transcription of the HIV-1 viral genome is mediated by the interaction of the viral protein Tat with the LTR and other transcriptional machinery. These specific interactions can be affected by the state of post-translational modifications on Tat. Previously, we have shown that Tat can be phosphorylated and acetylated in vivo resulting in an increase in the rate of transcription. In the present study, we investigated whether Tat could be methylated on lysine residues, specifically on lysine 50 and 51, and whether this modification resulted in a decrease of viral transcription from the LTR...
2008: Retrovirology
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