POU Domain Family Values: Flexibility, Partnerships, and Developmental Codes
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A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
Structure and Evolution of Four POU Domain Genes Expressed in Mouse Brain (POU Bnain-/POU Brain-2/POU Brain4/POU Scip/Homeobox) YOSHINOBU HARA*, ALESSANDRA C
Proc. Natl. Acad. Sci. USA Vol. 89, pp. 3280-3284, April 1992 Neurobiology Structure and evolution of four POU domain genes expressed in mouse brain (POU Bnain-/POU Brain-2/POU Brain4/POU Scip/homeobox) YOSHINOBU HARA*, ALESSANDRA C. ROVESCALLI, YONGSOK KIM, AND MARSHALL NIRENBERG Laboratory of Biochemical Genetics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 Contributed by Marshall Nirenberg, January 6, 1992 ABSTRACT Four mouse POU domain genomic DNA acid sequences of the proteins are related to one another and clones-Brain-i, Brain-2, Brain-4, and Scip-and Bran-2 suggests that the genes originated by duplication of an cDNA, which are expressed in adult brain, were cloned and the ancestral class III POU domain gene.t coding and noncoding regions ofthe genes were sequenced. The amino acid sequences of the four PoU domains are highly conserved; sequences in other regions of the proteins also are MATERIALS AND METHODS conserved but to a lesser extent. The absence of introns from DNA Coming and Sequencing. Our objective was to clone the coding regions of the four POU domain genes and the POU domain genes expressed in mouse brain. Mixtures of similarity of amino acid sequences of the corresponding pro- oligodeoxynucleotides that correspond to highly conserved teins suggest that the coding region of the ancestral class HI amino acid sequences in POU domains were used as primers POU domain gene lacked introns and therefore may have for amplification ofadult mouse brain POU domain cDNA by originated by reverse transcription of a molecule of POU PCR, and the amplified DNA fragments were cloned. -
Genome-Wide Association Analysis Reveal the Genetic Reasons Affect Melanin Spot Accumulation in Beak Skin of Ducks
Genome-wide association analysis reveal the genetic reasons affect melanin spot accumulation in beak skin of ducks Hehe Liu Sichuan Agricultural University Jianmei Wang Sichuan Agricultural University Jian Hu Chinese Academy of Agricultural Sciences Lei Wang Sichuan Agricultural University Zhanbao Guo Chinese Academy of Agricultural Sciences Wenlei Fan Chinese Academy of Agricultural Sciences Yaxi Xu Chinese Academy of Agricultural Sciences Dapeng Liu Chinese Academy of Agricultural Sciences Yunsheng Zhang Chinese Academy of Agricultural Sciences Ming Xie Chinese Academy of Agricultural Sciences Jing Tang Chinese Academy of Agricultural Sciences Wei Huang Chinese Academy of Agricultural Sciences Qi Zhang Chinese Academy of Agricultural Sciences Zhengkui Zhou Chinese Academy of Agricultural Sciences Shuisheng Hou ( [email protected] ) Chinese Academy of Agricultural Sciences Page 1/21 Research Article Keywords: skin melanin spot, duck, GWAS, genetic Posted Date: June 25th, 2021 DOI: https://doi.org/10.21203/rs.3.rs-608516/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 2/21 Abstract Background Skin pigmentation is a broadly appearing phenomenon of most animals and humans in nature. Here we used a bird model to investigate why melanin spot deposits on the skin. Results We result shown that melanin deposition in bird skin was induced by growth age and ultraviolet UV radiation and determined by genetic factors. GWAS helped us to identify two major loci affecting melanin deposition, located on chromosomes 13 and 25, respectively. Fine mapping works narrowed the candidate regions to 0.98 Mb and 1.0 Mb on chromosome 13 and 25, respectively. -
BRN2 Is a Transcriptional Repressor of CDH13 (T-Cadherin)
Laboratory Investigation (2012) 92, 1788–1800 & 2012 USCAP, Inc All rights reserved 0023-6837/12 $32.00 BRN2 is a transcriptional repressor of CDH13 (T-cadherin) in melanoma cells Lisa Ellmann1, Manjunath B Joshi2,3, Therese J Resink2, Anja K Bosserhoff1 and Silke Kuphal1 T-cadherin (cadherin 13, H-cadherin, gene name CDH13) has been proposed to act as a tumor-suppressor gene as its expression is significantly diminished in several types of carcinomas, including melanomas. Allelic loss and promoter hypermethylation have been proposed as mechanisms for silencing of CDH13. However, they do not account for loss of T-cadherin expression in all carcinomas, and other genetic or epigenetic alterations can be presumed. The present study investigated transcriptional regulation of CDH13 in melanoma. Bioinformatical analysis pointed to the presence of known BRN2 (also known as POU3F2 and N-Oct-3)-binding motifs in the CDH13 promoter sequence. We found an inverse correlation between BRN2 and T-cadherin protein and transcript expression. Reporter gene analysis and electrophoretic mobility shift assays in melanoma cells demonstrated that CDH13 is a direct target of BRN2 and that BRN2 is a functional transcriptional repressor of CDH13 promoter activity. The regulatory binding element of BRN2 was located À 219 bp of the CDH13 promoter proximal to the start codon and was identified as 50-CATGCAAAA-30. Ectopic expression of BRN2 in BRN2-negative/T-cadherin-positive melanoma cells resulted in suppression of CDH13 promoter activity, whereas BRN2 knockdown in BRN2-positive/T-cadherin-negative melanoma cells resulted in re-expression of T-cadherin transcripts and protein. -
Significance of Wilms' Tumor Gene 1 As a Biomarker in Acute Leukemia and Solid Tumors
UMEÅ UNIVERSITY MEDICAL DISSERTATIONS New Series No. 1799 ISSN 0346-6612 ISBN 978-91-7601-458-5 Significance of Wilms’ Tumor Gene 1 as a Biomarker in Acute Leukemia and Solid Tumors Charlotta Andersson Department of Medical Biosciences, Clinical Chemistry and Pathology Umeå University, Sweden Umeå 2016 Copyright © 2016 Charlotta Andersson ISBN: 978-91-7601-458-5 ISSN: 0346-6612 Printed by: Print & Media Umeå, Sweden, 2016 In memory of Aihong Li Table of Contents Table of Contents i Abstract iii Abbreviations iv List of Papers v Introduction 1 WT1 structure 1 WT1 target genes 3 WT1 protein partners 5 WT1 in normal and abnormal development 5 Hematopoiesis and WT1 7 WT1 as a tumor suppressor gene 7 WT1 as an oncogene or a chameleon gene 7 Acute leukemia (AL) and WT1 in AL 8 Renal cell carcinoma (RCC) and WT1 in RCC 13 Ovarian carcinoma (OC) and WT1 in OC 15 Aims of the Thesis 20 Materials and Methods 21 Patients and tissue samples (Papers I-IV) 21 Classification and risk group stratification in AL (Papers I and IV) 22 ccRCC grade and stage (Paper II) 22 OC classification, grade and stage (Paper III) 22 Genomic DNA preparation, RNA extraction and cDNA preparation (Papers I, II and IV) 23 Quantitative assessment of WT1 transcript expression with real-time quantitative PCR (RQ-PCR) (Papers I and II) 23 Sequencing analysis of the WT1 gene (Papers II and IV) 24 Immunohistochemistry (IHC) (Paper III) 24 Enzyme-linked immunosorbent assay (ELISA) (Paper III) 25 Statistical analysis 25 Results and Discussion 27 Paper I 27 Paper II 31 Paper III 35 Paper IV 38 Conclusions 42 Acknowledgments 44 References 47 i ii Abstract Wilms’ tumor gene 1 (WT1) is a zinc finger transcriptional regulator with crucial functions in embryonic development. -
Abnormal Mesenchymal Differentiation in the Superior Semicircular Canal of Brn4/Pou3f4 Knockout Mice
ORIGINAL ARTICLE 2 Abnormal Mesenchymal Differentiation in the Superior Semicircular Canal of Brn4/Pou3f4 Knockout Mice Steven E. Sobol, MD, MSc; Xiuyin Teng, MSc; E. Bryan Crenshaw III, PhD Objective: To examine the developmental time course of the SSCC in Brn4 knockout mice was initially detect- of the mutant phenotype and cellular mechanisms that able at P14. Interestingly, the mutant SSCC is indistin- result in malformations of the superior semicircular ca- guishable from control mice at earlier neonatal time points. nal (SSCC) in Brn4 knockout mice. Mutations in the Brn4/ In mutant neonates, there is persistence of immature wo- Pou3f4 gene result in characteristic inner ear abnormali- ven bone with high cellularity surrounding the perilym- ties in mutant mouse pedigrees, and the findings in these phatic space of the SSCC. These findings are not pres- mice are similar to those in human X-linked deafness type ent in control animal specimens, which demonstrate III. appropriate lamellar bony architecture. Design: Mutant and control mice were killed at vari- Conclusions: In Brn4 knockout mice, constriction of the ous neonatal time points to assess the development of SSCC with narrowing of the bony labyrinth develops in the SSCC. Measurements of SSCC diameter were made the postnatal period at approximately P14. The persis- on paint-perfused specimens at postnatal day (P) 0, P7, tence of immature bone in affected mice indicates that P10, and P14. Histologic evaluation of the SSCC was signaling abnormalities disrupt normal mesenchymal dif- made on hematoxylin-eosin–stained sections at P10. ferentiation in the SSCC. Results: A dysmorphic constriction of the superior arc Arch Otolaryngol Head Neck Surg. -
POU2F3 (NM 014352) Human Tagged ORF Clone Product Data
OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for RC210969L1 POU2F3 (NM_014352) Human Tagged ORF Clone Product data: Product Type: Expression Plasmids Product Name: POU2F3 (NM_014352) Human Tagged ORF Clone Tag: Myc-DDK Symbol: POU2F3 Synonyms: Epoc-1; OCT-11; OCT11; OTF-11; PLA-1; PLA1; Skn-1a Vector: pLenti-C-Myc-DDK (PS100064) E. coli Selection: Chloramphenicol (34 ug/mL) Cell Selection: None ORF Nucleotide The ORF insert of this clone is exactly the same as(RC210969). Sequence: Restriction Sites: SgfI-MluI Cloning Scheme: ACCN: NM_014352 ORF Size: 1308 bp This product is to be used for laboratory only. Not for diagnostic or therapeutic use. View online » ©2021 OriGene Technologies, Inc., 9620 Medical Center Drive, Ste 200, Rockville, MD 20850, US 1 / 2 POU2F3 (NM_014352) Human Tagged ORF Clone – RC210969L1 OTI Disclaimer: The molecular sequence of this clone aligns with the gene accession number as a point of reference only. However, individual transcript sequences of the same gene can differ through naturally occurring variations (e.g. polymorphisms), each with its own valid existence. This clone is substantially in agreement with the reference, but a complete review of all prevailing variants is recommended prior to use. More info OTI Annotation: This clone was engineered to express the complete ORF with an expression tag. Expression varies depending on the nature of the gene. RefSeq: NM_014352.1 RefSeq Size: 3013 bp RefSeq ORF: 1311 bp Locus ID: 25833 UniProt ID: Q9UKI9 MW: 47.4 kDa Gene Summary: This gene encodes a member of the POU domain family of transcription factors. -
Small Cell Lung Cancer: State of the Art of the Molecular and Genetic Landscape and Novel Perspective
cancers Review Small Cell Lung Cancer: State of the Art of the Molecular and Genetic Landscape and Novel Perspective Valeria Denninghoff 1 , Alessandro Russo 2,3 , Diego de Miguel-Pérez 2 , Umberto Malapelle 4 , Amin Benyounes 5, Allison Gittens 2, Andres Felipe Cardona 6,7,8 and Christian Rolfo 2,* 1 National Council for Scientific and Technical Research (CONICET), University of Buenos Aires, Buenos Aires C1122AAH, Argentina; [email protected] 2 Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA; [email protected] (A.R.); [email protected] (D.d.M.-P.); [email protected] (A.G.) 3 Medical Oncology Unit, A.O. Papardo, 98158 Messina, Italy 4 Department of Public Health, University of Naples Federico II, 80138 Naples, Italy; [email protected] 5 Thoracic Oncology, Inova Schar Cancer Center, Fairfax, VA 22031, USA; [email protected] 6 Clinical and Translational Oncology Group, Clínica del Country, Bogotá 110221, Colombia; [email protected] 7 Foundation for Clinical and Applied Cancer Research (FICMAC), Bogotá 110111, Colombia 8 Molecular Oncology and Biology Systems Research Group (Fox-G/ONCOLGroup), Universidad el Bosque, Bogotá 110121, Colombia * Correspondence: [email protected]; Tel.: +1-(410)-328-7224 Citation: Denninghoff, V.; Russo, A.; Simple Summary: Small cell lung cancer (SCLC) continues to carry a poor prognosis with a five-year de Miguel-Pérez, D.; Malapelle, U.; survival rate of 3.5% and a 10-year survival rate of 1.8%. The pathogenesis remains unclear, and Benyounes, A.; Gittens, A.; Cardona, there are no known predictive or diagnostic biomarkers. -
Lineage Transcription Factors Co-Regulate Subtype-Specific Genes Providing a Roadmap For
bioRxiv preprint doi: https://doi.org/10.1101/2020.08.13.249029; this version posted August 14, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Lineage transcription factors co-regulate subtype-specific genes providing a roadmap for systematic identification of small cell lung cancer vulnerabilities Karine Pozo1,2, Rahul K. Kollipara3, Demetra P. Kelenis1, Kathia E. Rodarte1, Xiaoyang Zhang4, John D. Minna5,6,7,8 and Jane E. Johnson1,6,8 1Department of Neuroscience, 2Department of Surgery, 3McDermott Center for Human Growth and Development, UT Southwestern Medical Center, Dallas, TX 75390, USA 4Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 5Hamon Center for Therapeutic Oncology Research, 6Simmons Comprehensive Cancer Center, 7Department of Internal Medicine, 8Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA JDM receives licensing fees for lung cancer lines from the NIH and UT Southwestern. 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.08.13.249029; this version posted August 14, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. ABSTRACT Lineage-defining transcription factors (LTFs) play key roles in tumor cell growth, making them highly attractive, but currently “undruggable”, small cell lung cancer (SCLC) vulnerabilities. -
Wilms' Tumor Gene 1 in Different Types of Cancer
UMEÅ UNIVERSITY MEDICAL DISSERTATIONS New Series No.1717 ISSN 0346-6612 ISBN 978-91-7601-263-5 Wilms’ tumor gene 1 in different types of cancer Xingru Li Department of Medical Biosciences, Clinical Chemistry Umeå University, Sweden Umeå 2015 Copyright © 2015 Xingru Li ISBN: 978-91-7601-263-5 ISSN: 0346-6612 Printed by: Print & Media Umeå, Sweden, 2015 To my family Table of Contents Abstract .......................................................................................................... 1 Original Articles ............................................................................................. 2 Abbreviations ................................................................................................. 3 Introduction .................................................................................................... 4 WT1 (Wilms’ tumor gene 1) ...................................................................... 4 Structure of WT1 ..................................................................................... 4 WT1, the transcription factor ................................................................. 5 WT1 and its interacting partners ............................................................ 5 WT1 function .......................................................................................... 8 The tumor suppressor ........................................................................ 8 An oncogene ...................................................................................... 8 Mutations and -
Chemical Agent and Antibodies B-Raf Inhibitor RAF265
Supplemental Materials and Methods: Chemical agent and antibodies B-Raf inhibitor RAF265 [5-(2-(5-(trifluromethyl)-1H-imidazol-2-yl)pyridin-4-yloxy)-N-(4-trifluoromethyl)phenyl-1-methyl-1H-benzp{D, }imidazol-2- amine] was kindly provided by Novartis Pharma AG and dissolved in solvent ethanol:propylene glycol:2.5% tween-80 (percentage 6:23:71) for oral delivery to mice by gavage. Antibodies to phospho-ERK1/2 Thr202/Tyr204(4370), phosphoMEK1/2(2338 and 9121)), phospho-cyclin D1(3300), cyclin D1 (2978), PLK1 (4513) BIM (2933), BAX (2772), BCL2 (2876) were from Cell Signaling Technology. Additional antibodies for phospho-ERK1,2 detection for western blot were from Promega (V803A), and Santa Cruz (E-Y, SC7383). Total ERK antibody for western blot analysis was K-23 from Santa Cruz (SC-94). Ki67 antibody (ab833) was from ABCAM, Mcl1 antibody (559027) was from BD Biosciences, Factor VIII antibody was from Dako (A082), CD31 antibody was from Dianova, (DIA310), and Cot antibody was from Santa Cruz Biotechnology (sc-373677). For the cyclin D1 second antibody staining was with an Alexa Fluor 568 donkey anti-rabbit IgG (Invitrogen, A10042) (1:200 dilution). The pMEK1 fluorescence was developed using the Alexa Fluor 488 chicken anti-rabbit IgG second antibody (1:200 dilution).TUNEL staining kits were from Promega (G2350). Mouse Implant Studies: Biopsy tissues were delivered to research laboratory in ice-cold Dulbecco's Modified Eagle Medium (DMEM) buffer solution. As the tissue mass available from each biopsy was limited, we first passaged the biopsy tissue in Balb/c nu/Foxn1 athymic nude mice (6-8 weeks of age and weighing 22-25g, purchased from Harlan Sprague Dawley, USA) to increase the volume of tumor for further implantation. -
The Oct1 Homolog Nubbin Is a Repressor of NF-Κb-Dependent Immune Gene Expression That Increases the Tolerance to Gut Microbiota
Dantoft et al. BMC Biology 2013, 11:99 http://www.biomedcentral.com/1741-7007/11/99 RESEARCH ARTICLE Open Access The Oct1 homolog Nubbin is a repressor of NF-κB-dependent immune gene expression that increases the tolerance to gut microbiota Widad Dantoft1, Monica M Davis1, Jessica M Lindvall2, Xiongzhuo Tang1, Hanna Uvell1,3, Anna Junell1, Anne Beskow1,4 and Ylva Engström1* Abstract Background: Innate immune responses are evolutionarily conserved processes that provide crucial protection against invading organisms. Gene activation by potent NF-κB transcription factors is essential both in mammals and Drosophila during infection and stress challenges. If not strictly controlled, this potent defense system can activate autoimmune and inflammatory stress reactions, with deleterious consequences for the organism. Negative regulation to prevent gene activation in healthy organisms, in the presence of the commensal gut flora, is however not well understood. Results: We show that the Drosophila homolog of mammalian Oct1/POU2F1 transcription factor, called Nubbin (Nub), is a repressor of NF-κB/Relish-driven antimicrobial peptide gene expression in flies. In nub1 mutants, which lack Nub-PD protein, excessive expression of antimicrobial peptide genes occurs in the absence of infection, leading to a significant reduction of the numbers of cultivatable gut commensal bacteria. This aberrant immune gene expression was effectively blocked by expression of Nub from a transgene. We have identified an upstream regulatory region, containing a cluster of octamer sites, which is required for repression of antimicrobial peptide gene expression in healthy flies. Chromatin immunoprecipitation experiments demonstrated that Nub binds to octamer-containing promoter fragments of several immune genes.