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Jordan Kardos, Shengjie Chai, Lisle E Mose, Sara R Selitsky, Bhavani Krishnan, Ryoichi Saito, Michael D Iglesia, Matthew I Milowsky, Joel S Parker, William Y Kim, Benjamin G Vincent
We report the discovery of a claudin-low molecular subtype of high-grade bladder cancer that shares characteristics with the homonymous subtype of breast cancer. Claudin-low bladder tumors were enriched for multiple genetic features including increased rates of RB1, EP300, and NCOR1 mutations; increased frequency of EGFR amplification; decreased rates of FGFR3, ELF3, and KDM6A mutations; and decreased frequency of PPARG amplification. While claudin-low tumors showed the highest expression of immune gene signatures, they also demonstrated gene expression patterns consistent with those observed in active immunosuppression...
March 17, 2016: JCI Insight
Glen M Scholz, Nur S Sulaiman, Sahar Al Baiiaty, Mei Qi Kwa, Eric C Reynolds
Keratinocytes are central to the barrier functions of surface epithelia, such as the gingiva and epidermis. RIPK4 is a key regulator of keratinocyte differentiation; however, the signalling pathways in which it functions remain poorly defined. In this study, we identified a regulatory relationship between RIPK4 and ELF3, an ETS family transcription factor. RIPK4 was shown to be important for the upregulation of ELF3 gene expression by the PKC agonist PMA in both oral and epidermal keratinocytes. RIPK4 promotes keratinocyte differentiation in part by phosphorylating and thereby activating the IRF6 transcription factor...
December 2016: Cellular Signalling
Vipulkumar Dadhania, Miao Zhang, Li Zhang, Jolanta Bondaruk, Tadeusz Majewski, Arlene Siefker-Radtke, Charles C Guo, Colin Dinney, David E Cogdell, Shizhen Zhang, Sangkyou Lee, June G Lee, John N Weinstein, Keith Baggerly, David McConkey, Bogdan Czerniak
BACKGROUND: It has been suggested that bladder cancer can be divided into two molecular subtypes referred to as luminal and basal with distinct clinical behaviors and sensitivities to chemotherapy. We aimed to validate these subtypes in several clinical cohorts and identify signature immunohistochemical markers that would permit simple and cost-effective classification of the disease in primary care centers. METHODS: We analyzed genomic expression profiles of bladder cancer in three cohorts of fresh frozen tumor samples: MD Anderson (n=132), Lund (n=308), and The Cancer Genome Atlas (TCGA) (n=408) to validate the expression signatures of luminal and basal subtypes and relate them to clinical follow-up data...
October 2016: EBioMedicine
Brett Ford, Weiwei Deng, Jenni Clausen, Sandra Oliver, Scott Boden, Megan Hemming, Ben Trevaskis
An increase in global temperatures will impact future crop yields. In the cereal crops wheat and barley, high temperatures accelerate reproductive development, reducing the number of grains per plant and final grain yield. Despite this relationship between temperature and cereal yield, it is not clear what genes and molecular pathways mediate the developmental response to increased temperatures. The plant circadian clock can respond to changes in temperature and is important for photoperiod-dependent flowering, and so is a potential mechanism controlling temperature responses in cereal crops...
October 2016: Journal of Experimental Botany
M Durán Aguilar, S I Román Ponce, F J Ruiz López, E González Padilla, C G Vásquez Peláez, A Bagnato, M G Strillacci
Mastitis, the most common and expensive disease in dairy cows, implies significant losses in the dairy industry worldwide. Many efforts have been made to improve genetic mastitis resistance in dairy populations, but low heritability of this trait made this process not as effective as desired. The purpose of this study was to identify genomic regions explaining genetic variation of somatic cell count using copy number variations (CNVs) as markers in the Holstein population, genotyped with the Illumina BovineHD BeadChip...
August 30, 2016: Journal of Animal Breeding and Genetics, Zeitschrift Für Tierzüchtung und Züchtungsbiologie
Maximilian O Press, Amy Lanctot, Christine Queitsch
Plants have evolved elaborate mechanisms controlling developmental responses to environmental stimuli. A particularly important stimulus is temperature. Previous work has identified the interplay of PIF4 and ELF3 as a central circuit underlying thermal responses in Arabidopsis thaliana. However, thermal responses vary widely among strains, possibly offering mechanistic insights into the wiring of this circuit. ELF3 contains a polyglutamine (polyQ) tract that is crucial for ELF3 function and varies in length across strains...
2016: PloS One
Chan Mi Lee, Jing Wu, Yi Xia, Jim Hu
E26 transformation-specific (Ets) family of transcription factors are characterized by the presence of Ets-DNA binding domain and have been found to be highly involved in hematopoiesis and various tissue differentiation. ESE-1, or Elf3 in mice, is a member of epithelium-specific Ets sub-family which is most prominently expressed in epithelial tissues such as the gut, mammary gland, and lung. The role of ESE-1 during embryogenesis had long been alluded from 30% fetal lethality in homozygous knockout mice and its high expression in preimplantation mouse embryos, but there has been no in-depth of analysis of ESE-1 function in early development...
2016: Frontiers in Cell and Developmental Biology
Yasuhito Sakuraba, Su-Hyun Han, Hyun-Jung Yang, Weilan Piao, Nam-Chon Paek
In Arabidopsis, EARLY FLOWERING3 (ELF3) has pivotal roles in controlling circadian rhythm and photoperiodic flowering. In addition, ELF3 negatively regulates leaf senescence by repressing the transcription of PHYTOCHROME-INTERACTING FACTOR4 (PIF4) and PHYTOCHROME-INTERACTING FACTOR5 (PIF5); elf3 mutants senesce earlier and ELF3-overexpressing (ELF3-OX) plants senesce later than wild type (WT). Here, we show that in contrast to Arabidopsis ELF3, which represses senescence, the rice homolog OsELF3.1 promotes leaf senescence; oself3...
September 2016: Plant Molecular Biology
Xianyong Gui, Ziran Meng, Yarrow J McConnell, Shuhong Liu, Vincent G Falck, Lloyd A Mack, Walley J Temple
BACKGROUND: Tumours of appendix, including classic carcinoid tumour (CCT), goblet cell carcinoid (GCC), low-grade appendiceal mucinous neoplasm, high-grade appendiceal mucinous neoplasm/mucinous carcinoma (MCA) and non-mucinous adenocarcinoma (NMA), show different and sometimes mixed morphological features. It was hypothesised that these tumours originate from common tumour stem cell(s) with potential of various cell lineage differentiation. In normal intestinal epithelium, absorptive lineage (enterocytes) differentiation is driven by Notch-Hes1 pathway, while secretory lineage is driven by Wnt-Math1 pathway and further separated by different downstream signallings into three sublineages (Gfi1-Klf4/Elf3 for goblet cells, Gfi1-Sox9 for Paneth cells and Ngn3-Pdx1/Beta2/Pax4 for enteroendocrine cells)...
July 1, 2016: Journal of Clinical Pathology
Miguel Otero, Haibing Peng, Karim El Hachem, Kirsty L Culley, Elisabeth B Wondimu, Justin Quinn, Hiroshi Asahara, Kaneyuki Tsuchimochi, Ko Hashimoto, Mary B Goldring
AIM: We showed previously that ELF3 protein levels are increased in osteoarthritic (OA) cartilage, that ELF3 accounts for inflammatory cytokine-driven MMP13 gene expression, and that, upon induction by IL-1β, ELF3 binds to the COL2A1 promoter and suppresses its activity in chondrocytes. Here, we aimed to further investigate the mechanism/s by which ELF3 represses COL2A1 transcription in chondrocytes. METHODS AND RESULTS: We report that ELF3 inhibits Sox9-driven COL2A1 promoter activity by interfering with the activator functions of CBP/300 and Sox9...
June 16, 2016: Connective Tissue Research
He Huang, Sophie Alvarez, Dmitri A Nusinow
Tandem affinity purification coupled with mass spectrometry (TAP-MS) analysis is a powerful biochemical approach to identify protein-protein associations. Here we describe two datasets generated by a series of TAP-MS analyses to co-purify proteins associated with either ELF3 or ELF4 of the Evening Complex (EC) ("Identification of Evening Complex Associated Proteins in Arabidopsis by Affinity Purification and Mass Spectrometry" (Huang et al., 2016a) [1]) or proteins associated with PCH1, which is a newly identified output of the circadian clock to regulate photoperiodic growth in Arabidopsis thaliana ("PCH1 integrates circadian and light-signaling pathways to control photoperiod-responsive growth in Arabidopsis" (Huang et al...
September 2016: Data in Brief
Javier Conde, Miguel Otero, Morena Scotece, Vanessa Abella, Verónica López, Jesús Pino, Rodolfo Gómez, Francisca Lago, Mary B Goldring, Oreste Gualillo
The E74-like factor 3 (ELF3) is a transcription factor induced by inflammatory cytokines in chondrocytes that increases gene expression of catabolic and inflammatory mediators. Lipocalin-2 (LCN2) is a novel adipokine that negatively impacts articular cartilage, triggering catabolic and inflammatory responses in chondrocytes. Here, we investigated the control of LCN2 gene expression by ELF3 in the context of IL-1-driven inflammatory responses in chondrocytes. The interaction of ELF3 and NFκB in modulating LCN2 levels was also explored...
May 25, 2016: Journal of Physiology
Minglei Zhang, Hongyan Li, Di Zou, Ji Gao
AIM: This study aimed to select several signature genes associated with bladder cancer, thus to investigate the possible mechanism in bladder cancer. METHODS: The mRNA expression profile data of GSE31614, including ten bladder tissues and ten control samples, was downloaded from the Gene Expression Omnibus. The differentially expressed genes (DEGs) in bladder cancer samples compared with the control samples were screened using the Student's t-test method. Functional analysis for the DEGs was analyzed using the Database for Annotation, Visualization, and Integrated Discovery from the Gene Ontology database, followed by the transcription function annotation of DEGs from Tumor-Associated Gene database...
2016: OncoTargets and Therapy
M A Alvarez, G Tranquilli, S Lewis, N Kippes, J Dubcovsky
Wheat cultivars exposed to optimal photoperiod and vernalization treatments still exhibit differences in flowering time, referred to as earliness per se (Eps). We previously identified the Eps-A (m) 1 locus from Triticum monococcum and showed that the allele from cultivated accession DV92 significantly delays heading time and increases the number of spikelets per spike relative to the allele from wild accession G3116. Here, we expanded a high-density genetic and physical map of the Eps-A (m) 1 region and identified the wheat ortholog of circadian clock regulator EARLY FLOWERING 3 (ELF3) as a candidate gene...
July 2016: Functional & Integrative Genomics
Kyung Jun Lee, Dong Sub Kim, Jin-Baek Kim, Sung-Hwan Jo, Si-Yong Kang, Hong-Il Choi, Bo-Keun Ha
Flowering is indicative of the transition from vegetative to reproductive phase, a critical event in the life cycle of plants. In this study, we performed whole genome resequencing by Illumina HiSeq to identify changes in flowering genes using an early-flowering phenotype of soybean mutant line Josaengserori (JS) derived from Korean landrace, Seoritae (SR), and we obtained mapped reads of 131,769,690 and 167,669,640 bp in JS and SR, respectively. From the whole genome sequencing results between JS and SR, we identified 332,821 polymorphic SNPs and 65,178 indels, respectively...
August 2016: Molecular Genetics and Genomics: MGG
Syed A Ali, Verline Justilien, Lee Jamieson, Nicole R Murray, Alan P Fields
We report that the protein kinase Cι (PKCι) oncogene controls expression of NOTCH3, a key driver of stemness, in KRAS-mediated lung adenocarcinoma (LADC). PKCι activates NOTCH3 expression by phosphorylating the ELF3 transcription factor and driving ELF3 occupancy on the NOTCH3 promoter. PKCι-ELF3-NOTCH3 signaling controls the tumor-initiating cell phenotype by regulating asymmetric cell division, a process necessary for tumor initiation and maintenance. Primary LADC tumors exhibit PKCι-ELF3-NOTCH3 signaling, and combined pharmacologic blockade of PKCι and NOTCH synergistically inhibits tumorigenic behavior in vitro and LADC growth in vivo demonstrating the therapeutic potential of PKCι-ELF3-NOTCH3 signal inhibition to more effectively treat KRAS LADC...
March 14, 2016: Cancer Cell
Dongqing Xu, Danmeng Zhu, Xing Wang Deng
Plants use the circadian clock as a timekeeping mechanism to regulate photoperiodic flowering in response to the seasonal changes. CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1), initially identified as a central repressor of seedling photomorphogenesis, was recently shown to be involved in the regulation of light input to the circadian clock, modulating the circadian rhythm and flowering. COP1 encodes a RING-finger E3 ubiquitin ligase and works in concert with SUPPRESSOR of phyA-105 (SPA) proteins to repress photoperiodic flowering by regulating proteasome-mediated degradation of CONSTANS (CO), a central regulator of photoperiodic flowering...
2016: F1000Research
Vijaya Narasihma Reddy Gajulapalli, Venkata Subramanyam Kumar Samanthapudi, Madhusudana Pulaganti, Saratchandra Singh Khumukcham, Vijaya Lakhsmi Malisetty, Lalitha Guruprasad, Suresh Kumar Chitta, Bramanandam Manavathi
Oestrogen receptor-α (ERα) is a ligand-dependent transcription factor that primarily mediates oestrogen (E2)-dependent gene transcription required for mammary gland development. Coregulators critically regulate ERα transcription functions by directly interacting with it. In the present study, we report that ELF3, an epithelial-specific ETS transcription factor, acts as a transcriptional repressor of ERα. Co-immunoprecipitation (Co-IP) analysis demonstrated that ELF3 strongly binds to ERα in the absence of E2, but ELF3 dissociation occurs upon E2 treatment in a dose- and time-dependent manner suggesting that E2 negatively influences such interaction...
April 15, 2016: Biochemical Journal
Shinichi Yachida, Laura D Wood, Masami Suzuki, Erina Takai, Yasushi Totoki, Mamoru Kato, Claudio Luchini, Yasuhito Arai, Hiromi Nakamura, Natsuko Hama, Asmaa Elzawahry, Fumie Hosoda, Tomoki Shirota, Nobuhiko Morimoto, Kunio Hori, Jun Funazaki, Hikaru Tanaka, Chigusa Morizane, Takuji Okusaka, Satoshi Nara, Kazuaki Shimada, Nobuyoshi Hiraoka, Hirokazu Taniguchi, Ryota Higuchi, Minoru Oshima, Keiichi Okano, Seiko Hirono, Masamichi Mizuma, Koji Arihiro, Masakazu Yamamoto, Michiaki Unno, Hiroki Yamaue, Matthew J Weiss, Christopher L Wolfgang, Toru Furukawa, Hitoshi Nakagama, Bert Vogelstein, Tohru Kiyono, Ralph H Hruban, Tatsuhiro Shibata
Ampullary carcinomas are highly malignant neoplasms that can have either intestinal or pancreatobiliary differentiation. To characterize somatic alterations in ampullary carcinomas, we performed whole-exome sequencing and DNA copy-number analysis on 60 ampullary carcinomas resected from clinically well-characterized Japanese and American patients. We next selected 92 genes and performed targeted sequencing to validate significantly mutated genes in an additional 112 cancers. The prevalence of driver gene mutations in carcinomas with the intestinal phenotype is different from those with the pancreatobiliary phenotype...
February 8, 2016: Cancer Cell
Marie-Claude Gingras, Kyle R Covington, David K Chang, Lawrence A Donehower, Anthony J Gill, Michael M Ittmann, Chad J Creighton, Amber L Johns, Eve Shinbrot, Ninad Dewal, William E Fisher, Christian Pilarsky, Robert Grützmann, Michael J Overman, Nigel B Jamieson, George Van Buren, Jennifer Drummond, Kimberly Walker, Oliver A Hampton, Liu Xi, Donna M Muzny, Harsha Doddapaneni, Sandra L Lee, Michelle Bellair, Jianhong Hu, Yi Han, Huyen H Dinh, Mike Dahdouli, Jaswinder S Samra, Peter Bailey, Nicola Waddell, John V Pearson, Ivon Harliwong, Huamin Wang, Daniela Aust, Karin A Oien, Ralph H Hruban, Sally E Hodges, Amy McElhany, Charupong Saengboonmee, Fraser R Duthie, Sean M Grimmond, Andrew V Biankin, David A Wheeler, Richard A Gibbs
The ampulla of Vater is a complex cellular environment from which adenocarcinomas arise to form a group of histopathologically heterogenous tumors. To evaluate the molecular features of these tumors, 98 ampullary adenocarcinomas were evaluated and compared to 44 distal bile duct and 18 duodenal adenocarcinomas. Genomic analyses revealed mutations in the WNT signaling pathway among half of the patients and in all three adenocarcinomas irrespective of their origin and histological morphology. These tumors were characterized by a high frequency of inactivating mutations of ELF3, a high rate of microsatellite instability, and common focal deletions and amplifications, suggesting common attributes in the molecular pathogenesis are at play in these tumors...
February 2, 2016: Cell Reports
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