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Xiao-Ping Chen, Hao Zheng, Wen-Ge Li, Guo-Dong Chen, Jin-Xing Lu
Systemic bacterial infections are prone to secondary Candida albicans super-infection. However, the molecular mechanisms involved remain poorly understood. In this study, a model comprising sublethal cecal ligation and puncture plus C. albicans intravenous injection was applied to mimic the situation in super-infection. Compared with mice without systemic bacterial infection, mice with systemic bacterial infection had lower antifungal gene expression (including Il1b, Tnf, Il6, Ifnb, Ifng, Cxcl1, and Ccr2) in monocytes and less inflammatory monocytes and neutrophils infiltrating into the kidney when challenged with C...
May 11, 2018: Cellular Microbiology
Chiou-Hong Lin, Stephen Hon-Kit Wong, Jason H Kurzer, Corina Schneidawind, Michael C Wei, Jesús Duque-Afonso, Johan Jeong, Xuhui Feng, Michael L Cleary
Acute lymphoblastic leukemia (ALL) is associated with significant morbidity and mortality, necessitating further improvements in diagnosis and therapy. Targeted therapies directed against chromatin regulators are emerging as promising approaches in preclinical studies and early clinical trials. Here, we demonstrate an oncogenic role for the protein lysine methyltransferase SETDB2 in leukemia pathogenesis. It is overexpressed in pre-BCR+ ALL and required for their maintenance in vitro and in vivo. SETDB2 expression is maintained as a direct target gene of the chimeric transcription factor E2A-PBX1 in a subset of ALL and suppresses expression of the cell-cycle inhibitor CDKN2C through histone H3K9 tri-methylation, thus establishing an oncogenic pathway subordinate to E2A-PBX1 that silences a major tumor suppressor in ALL...
April 24, 2018: Cell Reports
Abdullah Al Emran, Diego M Marzese, Dinoop Ravindran Menon, Mitchell S Stark, Joachim Torrano, Heinz Hammerlindl, Gao Zhang, Patricia Brafford, Matthew P Salomon, Nellie Nelson, Sabrina Hammerlindl, Deepesh Gupta, Gordon B Mills, Yiling Lu, Richard A Sturm, Keith Flaherty, Dave S B Hoon, Brian Gabrielli, Meenhard Herlyn, Helmut Schaider
Besides somatic mutations or drug efflux, epigenetic reprogramming can lead to acquired drug resistance. We recently have identified early stress-induced multi-drug tolerant cancer cells termed induced drug-tolerant cells (IDTCs). Here, IDTCs were generated using different types of cancer cell lines; melanoma, lung, breast and colon cancer. A common loss of the H3K4me3 and H3K27me3 and gain of H3K9me3 mark was observed as a significant response to drug exposure or nutrient starvation in IDTCs. These epigenetic changes were reversible upon drug holidays...
February 2, 2018: Oncotarget
Bernard Crespi, Silven Read, Peter Hurd
The gene SETDB2, which mediates aspects of laterality in animal model systems, has recently been linked with human handedness as measured continuously on a scale from strong left to strong right. By contrast, it was marginally associated with a left-right dichotomous measure, and it showed no evidence of association with absolute handedness strength independent of direction. We genotyped the SETDB2 handedness-associated single nucleotide polymorphism, rs4942830, in a large healthy population likewise phenotyped for continuous, absolute, and dichotomous handedness variables...
January 2018: Heredity
Maria João Ferreira, Ana Sílvia Pires-Luís, Márcia Vieira-Coimbra, Pedro Costa-Pinheiro, Luís Antunes, Paula C Dias, Francisco Lobo, Jorge Oliveira, Céline S Gonçalves, Bruno M Costa, Rui Henrique, Carmen Jerónimo
Increasing detection of small renal masses by imaging techniques entails the need for accurate discrimination between benign and malignant renal cell tumors (RCTs) as well as among malignant RCTs, owing to differential risk of progression through metastization. Although histone methylation has been implicated in renal tumorigenesis, its potential as biomarker for renal cell carcinoma (RCC) progression remains largely unexplored. Thus, we aimed to characterize the differential expression of histone methyltransferases (HMTs) and histone demethylases (HDMs) in RCTs to assess their potential as metastasis biomarkers...
2017: Epigenetics: Official Journal of the DNA Methylation Society
Craig L Parfett, Daniel Desaulniers
An emerging vision for toxicity testing in the 21st century foresees in vitro assays assuming the leading role in testing for chemical hazards, including testing for carcinogenicity. Toxicity will be determined by monitoring key steps in functionally validated molecular pathways, using tests designed to reveal chemically-induced perturbations that lead to adverse phenotypic endpoints in cultured human cells. Risk assessments would subsequently be derived from the causal in vitro endpoints and concentration vs...
June 1, 2017: International Journal of Molecular Sciences
Vinay Kumar Rao, Ananya Pal, Reshma Taneja
Progression of cells through distinct phases of the cell cycle, and transition into out-of-cycling states, such as terminal differentiation and senescence, is accompanied by specific patterns of gene expression. These cell fate decisions are mediated not only by distinct transcription factors, but also chromatin modifiers that establish heritable epigenetic patterns. Lysine methyltransferases (KMTs) that mediate methylation marks on histone and non-histone proteins are now recognized as important regulators of gene expression in cycling and non-cycling cells...
March 4, 2017: Epigenetics: Official Journal of the DNA Methylation Society
Fang-Nong Lai, Hong-Li Zhai, Ming Cheng, Jun-Yu Ma, Shun-Feng Cheng, Wei Ge, Guo-Liang Zhang, Jun-Jie Wang, Rui-Qian Zhang, Xue Wang, Ling-Jiang Min, Jiu-Zhou Song, Wei Shen
Dairy goats are one of the most utilized domesticated animals in China. Here, we selected extreme populations based on differential fecundity in two Laoshan dairy goat populations. Utilizing deep sequencing we have generated 68.7 and 57.8 giga base of sequencing data, and identified 12,458,711 and 12,423,128 SNPs in the low fecundity and high fecundity groups, respectively. Following selective sweep analyses, a number of loci and candidate genes in the two populations were scanned independently. The reproduction related genes CCNB2, AR, ADCY1, DNMT3B, SMAD2, AMHR2, ERBB2, FGFR1, MAP3K12 and THEM4 were specifically selected in the high fecundity group whereas KDM6A, TENM1, SWI5 and CYM were specifically selected in the low fecundity group...
December 1, 2016: Scientific Reports
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...
October 11, 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...
July 11, 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.
January 2017: 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...
March 15, 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 Swaminanthan, 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
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