E Proteins and ID Proteins: Helix-Loop-Helix Partners in Development and Disease
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Novel TAL1 Targets Beyond Protein-Coding Genes: Identification of TAL1-Regulated Micrornas in T-Cell Acute Lymphoblastic Leukemia
Letters to the Editor 1603 REFERENCES 8 Yoshida K, Sanada M, Shiraishi Y, Nowak D, Nagata Y, Yamamoto R et al. Frequent 1 Rozman C, Montserrat E. Chronic lymphocytic leukemia. N Engl J Med 1995; 333: pathway mutations of splicing machinery in myelodysplasia. Nature 2011; 478: 64–69. 1052–1057. 9 Papaemmanuil E, Cazzola M, Boultwood J, Malcovati L, Vyas P, Bowen D et al. 2 Zenz T, Mertens D, Kuppers R, Dohner H, Stilgenbauer S. From pathogenesis to Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts. N Engl J Med treatment of chronic lymphocytic leukaemia. Nat Rev Cancer 2010; 10: 37–50. 2011; 365: 1384–1395. 3 Puente XS, Pinyol M, Quesada V, Conde L, Ordonez GR, Villamor N et al. Whole- 10 Damm F, Nguyen-Khac F, Fontenay M, Bernard OA. Spliceosome and other novel genome sequencing identifies recurrent mutations in chronic lymphocytic leu- mutations in chronic lymphocytic leukemia and myeloid malignancies. Leukemia kaemia. Nature 2011; 475: 101–105. 2012; 26: 2027–2031. 4 Quesada V, Conde L, Villamor N, Ordonez GR, Jares P, Bassaganyas L et al. Exome 11 Wahl MC, Will CL, Luhrmann R. The spliceosome: design principles of a dynamic sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in RNP machine. Cell 2009; 136: 701–718. chronic lymphocytic leukemia. Nat Genet 2012; 44: 47–52. 12 David CJ, Manley JL. Alternative pre-mRNA splicing regulation in cancer: pathways 5 Wang L, Lawrence MS, Wan Y, Stojanov P, Sougnez C, Stevenson K et al. SF3B1 and programs unhinged. Genes Dev 2010; 24: 2343–2364. -
Activated Peripheral-Blood-Derived Mononuclear Cells
Transcription factor expression in lipopolysaccharide- activated peripheral-blood-derived mononuclear cells Jared C. Roach*†, Kelly D. Smith*‡, Katie L. Strobe*, Stephanie M. Nissen*, Christian D. Haudenschild§, Daixing Zhou§, Thomas J. Vasicek¶, G. A. Heldʈ, Gustavo A. Stolovitzkyʈ, Leroy E. Hood*†, and Alan Aderem* *Institute for Systems Biology, 1441 North 34th Street, Seattle, WA 98103; ‡Department of Pathology, University of Washington, Seattle, WA 98195; §Illumina, 25861 Industrial Boulevard, Hayward, CA 94545; ¶Medtronic, 710 Medtronic Parkway, Minneapolis, MN 55432; and ʈIBM Computational Biology Center, P.O. Box 218, Yorktown Heights, NY 10598 Contributed by Leroy E. Hood, August 21, 2007 (sent for review January 7, 2007) Transcription factors play a key role in integrating and modulating system. In this model system, we activated peripheral-blood-derived biological information. In this study, we comprehensively measured mononuclear cells, which can be loosely termed ‘‘macrophages,’’ the changing abundances of mRNAs over a time course of activation with lipopolysaccharide (LPS). We focused on the precise mea- of human peripheral-blood-derived mononuclear cells (‘‘macro- surement of mRNA concentrations. There is currently no high- phages’’) with lipopolysaccharide. Global and dynamic analysis of throughput technology that can precisely and sensitively measure all transcription factors in response to a physiological stimulus has yet to mRNAs in a system, although such technologies are likely to be be achieved in a human system, and our efforts significantly available in the near future. To demonstrate the potential utility of advanced this goal. We used multiple global high-throughput tech- such technologies, and to motivate their development and encour- nologies for measuring mRNA levels, including massively parallel age their use, we produced data from a combination of two distinct signature sequencing and GeneChip microarrays. -
DNA·RNA Triple Helix Formation Can Function As a Cis-Acting Regulatory
DNA·RNA triple helix formation can function as a cis-acting regulatory mechanism at the human β-globin locus Zhuo Zhoua, Keith E. Gilesa,b,c, and Gary Felsenfelda,1 aLaboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892; bUniversity of Alabama at Birmingham Stem Cell Institute, University of Alabama at Birmingham, Birmingham, AL 35294; and cDepartment of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294 Contributed by Gary Felsenfeld, February 4, 2019 (sent for review January 4, 2019; reviewed by James Douglas Engel and Sergei M. Mirkin) We have identified regulatory mechanisms in which an RNA tran- of the criteria necessary to establish the presence of a triplex script forms a DNA duplex·RNA triple helix with a gene or one of its structure, we first describe and characterize triplex formation at regulatory elements, suggesting potential auto-regulatory mecha- the FAU gene in human erythroid K562 cells. FAU encodes a nisms in vivo. We describe an interaction at the human β-globin protein that is a fusion containing fubi, a ubiquitin-like protein, locus, in which an RNA segment embedded in the second intron of and ribosomal protein S30. Although fubi function is unknown, the β-globin gene forms a DNA·RNA triplex with the HS2 sequence posttranslational processing produces S30, a component of the within the β-globin locus control region, a major regulator of glo- 40S ribosome. We used this system to refine methods necessary bin expression. We show in human K562 cells that the triplex is to detect triplex formation and to distinguish it from R-loop stable in vivo. -
An Animal Model with a Cardiomyocyte-Specific Deletion of Estrogen Receptor Alpha: Functional, Metabolic, and Differential Netwo
Washington University School of Medicine Digital Commons@Becker Open Access Publications 2014 An animal model with a cardiomyocyte-specific deletion of estrogen receptor alpha: Functional, metabolic, and differential network analysis Sriram Devanathan Washington University School of Medicine in St. Louis Timothy Whitehead Washington University School of Medicine in St. Louis George G. Schweitzer Washington University School of Medicine in St. Louis Nicole Fettig Washington University School of Medicine in St. Louis Attila Kovacs Washington University School of Medicine in St. Louis See next page for additional authors Follow this and additional works at: https://digitalcommons.wustl.edu/open_access_pubs Recommended Citation Devanathan, Sriram; Whitehead, Timothy; Schweitzer, George G.; Fettig, Nicole; Kovacs, Attila; Korach, Kenneth S.; Finck, Brian N.; and Shoghi, Kooresh I., ,"An animal model with a cardiomyocyte-specific deletion of estrogen receptor alpha: Functional, metabolic, and differential network analysis." PLoS One.9,7. e101900. (2014). https://digitalcommons.wustl.edu/open_access_pubs/3326 This Open Access Publication is brought to you for free and open access by Digital Commons@Becker. It has been accepted for inclusion in Open Access Publications by an authorized administrator of Digital Commons@Becker. For more information, please contact [email protected]. Authors Sriram Devanathan, Timothy Whitehead, George G. Schweitzer, Nicole Fettig, Attila Kovacs, Kenneth S. Korach, Brian N. Finck, and Kooresh I. Shoghi This open access publication is available at Digital Commons@Becker: https://digitalcommons.wustl.edu/open_access_pubs/3326 An Animal Model with a Cardiomyocyte-Specific Deletion of Estrogen Receptor Alpha: Functional, Metabolic, and Differential Network Analysis Sriram Devanathan1, Timothy Whitehead1, George G. Schweitzer2, Nicole Fettig1, Attila Kovacs3, Kenneth S. -
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. -
Steroid-Dependent Regulation of the Oviduct: a Cross-Species Transcriptomal Analysis
University of Kentucky UKnowledge Theses and Dissertations--Animal and Food Sciences Animal and Food Sciences 2015 Steroid-dependent regulation of the oviduct: A cross-species transcriptomal analysis Katheryn L. Cerny University of Kentucky, [email protected] Right click to open a feedback form in a new tab to let us know how this document benefits ou.y Recommended Citation Cerny, Katheryn L., "Steroid-dependent regulation of the oviduct: A cross-species transcriptomal analysis" (2015). Theses and Dissertations--Animal and Food Sciences. 49. https://uknowledge.uky.edu/animalsci_etds/49 This Doctoral Dissertation is brought to you for free and open access by the Animal and Food Sciences at UKnowledge. It has been accepted for inclusion in Theses and Dissertations--Animal and Food Sciences by an authorized administrator of UKnowledge. For more information, please contact [email protected]. STUDENT AGREEMENT: I represent that my thesis or dissertation and abstract are my original work. Proper attribution has been given to all outside sources. I understand that I am solely responsible for obtaining any needed copyright permissions. I have obtained needed written permission statement(s) from the owner(s) of each third-party copyrighted matter to be included in my work, allowing electronic distribution (if such use is not permitted by the fair use doctrine) which will be submitted to UKnowledge as Additional File. I hereby grant to The University of Kentucky and its agents the irrevocable, non-exclusive, and royalty-free license to archive and make accessible my work in whole or in part in all forms of media, now or hereafter known. -
Transcritional Regulatory Networks Downstream of TAL1/SCL in T-Cell Acute Lymphoblastic Leukemia
Supplemental Materials Transcritional Regulatory Networks Downstream of TAL1/SCL in T-cell Acute Lymphoblastic Leukemia Palomero et al. Figure S1. Downregulation of TAL1 by RNA interference does not affect apoptosis in Jurkat cells. Figure S2. Scatter plots of Chromatin immunoprecipitations performed with TAL1#370 antibody in Jurkat cells. Figure S3. Target validation by gene-specific quantitative RT-PCR (qRT-PCR) Table S1. Genes regulated by TAL1 knockdown are identified as direct targets of this transcription factor using ChIP on chip. Table S2. Analysis of TAL1, E2A and HEB binding to TAL1 direct targets identified by ChIP on chip. Table S3. Previously described TAL1 targets. Figure S1. Downregulation of TAL1 by RNA interference does not affect apoptosis in Jurkat cells. Annexin V staining was used to quantify apoptosis rates in Jurkat cell clones expressing TAL1 shRNA (right panels) or a control shRNA (left panels). The percentage of apoptotic cells is indicated in the bottom right corner of each graph, while the dead cell percentage is indicated in the top right corner. PI: propidium iodide. Name Description p-value IFRD1 interferon-related developmental regulator 1 0.009927703 PCK2 phosphoenolpyruvate carboxykinase 2 (mitochondrial) 0.00445631 ATRX alpha thalassemia/mental retardation syndrome X-linked (RAD54 homolog, S. cerevisiae) 0.010847575 CDK6 cyclin-dependent kinase 6 0.044093956 Table S1. Genes regulated by TAL1 knockdown are identified as direct target of this transcription factor using ChIP on chip. The p-value determined by the error model applied to the ChIP on chip fluorescence data is indicated in the right column. Name Description Name Description E2A E2A HEB HEB TAL1 TAL1 Signal transduction-Receptor Transporters-lipids/small molecules MUC16 mucin 16 ABCC12 ATP-binding cassette, sub-fam. -
Function of Bromodomain and Extra-Terminal Motif Proteins (Bets) in Gata1-Mediated Transcription
University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2015 Function of Bromodomain and Extra-Terminal Motif Proteins (bets) in Gata1-Mediated Transcription Aaron James Stonestrom University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Molecular Biology Commons, and the Pharmacology Commons Recommended Citation Stonestrom, Aaron James, "Function of Bromodomain and Extra-Terminal Motif Proteins (bets) in Gata1-Mediated Transcription" (2015). Publicly Accessible Penn Dissertations. 1148. https://repository.upenn.edu/edissertations/1148 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/1148 For more information, please contact [email protected]. Function of Bromodomain and Extra-Terminal Motif Proteins (bets) in Gata1-Mediated Transcription Abstract Bromodomain and Extra-Terminal motif proteins (BETs) associate with acetylated histones and transcription factors. While pharmacologic inhibition of this ubiquitous protein family is an emerging therapeutic approach for neoplastic and inflammatory disease, the mechanisms through which BETs act remain largely uncharacterized. Here we explore the role of BETs in the physiologically relevant context of erythropoiesis driven by the transcription factor GATA1. First, we characterize functions of the BET family as a whole using a pharmacologic approach. We find that BETs are broadly required for GATA1-mediated transcriptional activation, but that repression is largely BET-independent. BETs support activation by facilitating both GATA1 occupancy and transcription downstream of its binding. Second, we test the specific olesr of BETs BRD2, BRD3, and BRD4 in GATA1-activated transcription. BRD2 and BRD4 are required for efficient anscriptionaltr activation by GATA1. Despite co-localizing with the great majority of GATA1 binding sites, we find that BRD3 is not equirr ed for GATA1-mediated transcriptional activation. -
Paracrine Activation of WNT/Β-Catenin Pathway in Uterine Leiomyoma Stem Cells Promotes Tumor Growth
Paracrine activation of WNT/β-catenin pathway in uterine leiomyoma stem cells promotes tumor growth Masanori Onoa,b, Ping Yina, Antonia Navarroa, Molly B. Moraveka, John S. Coon Va, Stacy A. Druschitza, Vanida Ann Sernaa, Wenan Qianga, David C. Brooksa, Saurabh S. Malpania, Jiajia Maa, Cihangir Mutlu Ercana, Navdha Mittala, Diana Monsivaisa, Matthew T. Dysona, Alex Yemelyanovc, Tetsuo Maruyamab, Debabrata Chakravartia, J. Julie Kima, Takeshi Kuritaa, Cara J. Gottardic, and Serdar E. Buluna,1 Departments of aObstetrics and Gynecology and cMedicine, Feinberg School of Medicine at Northwestern University, Chicago, IL 60611; and bDepartment of Obstetrics and Gynecology, Keio University School of Medicine, Shinjuku, Tokyo 160-8582, Japan Edited by Jan-Åke Gustafsson, University of Houston, Houston, Texas, and approved September 5, 2013 (received for review July 18, 2013) Uterine leiomyomas are extremely common estrogen and proges- somatic stem cells and has been used to isolate them from many terone-dependent tumors of the myometrium and cause irregular adult tissues, such as the myometrium, endometrium, and mam- – uterine bleeding, severe anemia, and recurrent pregnancy loss in mary gland (9 12). We and another group have reported that SP 15–30% of reproductive-age women. Each leiomyoma is thought cells from human LM exhibit key features of the tumor-initiating to arise from a single mutated myometrial smooth muscle stem cells (13, 14). It has been proposed that each LM originates from a single cell. Leiomyoma side-population (LMSP) cells comprising 1% of all transformed somatic stem cell of the myometrium in an ovarian tumor cells and displaying tumor-initiating stem cell characteristics steroid-dependent manner (15); however, this suggestion has not are essential for estrogen- and progesterone-dependent in vivo been proven definitively. -
ARID5B As a Critical Downstream Target of the TAL1 Complex That Activates the Oncogenic Transcriptional Program and Promotes T-Cell Leukemogenesis
Downloaded from genesdev.cshlp.org on October 10, 2021 - Published by Cold Spring Harbor Laboratory Press ARID5B as a critical downstream target of the TAL1 complex that activates the oncogenic transcriptional program and promotes T-cell leukemogenesis Wei Zhong Leong,1 Shi Hao Tan,1 Phuong Cao Thi Ngoc,1 Stella Amanda,1 Alice Wei Yee Yam,1 Wei-Siang Liau,1 Zhiyuan Gong,2 Lee N. Lawton,1 Daniel G. Tenen,1,3,4 and Takaomi Sanda1,4 1Cancer Science Institute of Singapore, National University of Singapore, 117599 Singapore; 2Department of Biological Sciences, National University of Singapore, 117543 Singapore; 3Harvard Medical School, Boston, Massachusetts 02215, USA; 4Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 117599 Singapore The oncogenic transcription factor TAL1/SCL induces an aberrant transcriptional program in T-cell acute lym- phoblastic leukemia (T-ALL) cells. However, the critical factors that are directly activated by TAL1 and contribute to T-ALL pathogenesis are largely unknown. Here, we identified AT-rich interactive domain 5B (ARID5B) as a col- laborating oncogenic factor involved in the transcriptional program in T-ALL. ARID5B expression is down-regulated at the double-negative 2–4 stages in normal thymocytes, while it is induced by the TAL1 complex in human T-ALL cells. The enhancer located 135 kb upstream of the ARID5B gene locus is activated under a superenhancer in T-ALL cells but not in normal T cells. Notably, ARID5B-bound regions are associated predominantly with active tran- scription. ARID5B and TAL1 frequently co-occupy target genes and coordinately control their expression. -
Modeling the Phenotype of Spinal Muscular Atrophy by the Direct Conversion of Human Fibroblasts to Motor Neurons
www.impactjournals.com/oncotarget/ Oncotarget, 2017, Vol. 8, (No. 7), pp: 10945-10953 Research Paper Modeling the phenotype of spinal muscular atrophy by the direct conversion of human fibroblasts to motor neurons Qi-Jie Zhang1,*, Jin-Jing Li1,*, Xiang Lin1, Ying-Qian Lu1, Xin-Xin Guo1, En-Lin Dong1, Miao Zhao1, Jin He1, Ning Wang1,2 and Wan-Jin Chen1,2 1 Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China 2 Fujian Key Laboratory of Molecular Neurology, Fuzhou, China * These authors have contributed equally to this work Correspondence to: Wan-Jin Chen, email: [email protected] Keywords: direct reprogramming; fibroblast; induced motor neuron; spinal muscular atrophy Received: June 08, 2016 Accepted: November 22, 2016 Published: January 13, 2017 ABSTRACT Spinal muscular atrophy (SMA) is a lethal autosomal recessive neurological disease characterized by selective degeneration of motor neurons in the spinal cord. In recent years, the development of cellular reprogramming technology has provided an alternative and effective method for obtaining patient-specific neuronsin vitro. In the present study, we applied this technology to the field of SMA to acquire patient- specific induced motor neurons that were directly converted from fibroblasts via the forced expression of 8 defined transcription factors. The infected fibroblasts began to grow in a dipolar manner, and the nuclei gradually enlarged. Typical Tuj1-positive neurons were generated at day 23. After day 35, induced neurons with multiple neurites were observed, and these neurons also expressed the hallmarks of Tuj1, HB9, ISL1 and CHAT. The conversion efficiencies were approximately 5.8% and 5.5% in the SMA and control groups, respectively. -
1 Original Article Scleraxis and E47 Cooperatively Regulate the Sox9
Original article Scleraxis and E47 cooperatively regulate the Sox9-dependent transcription Takayuki Furumatsu a, *, Chisa Shukunami b, Michiyo Amemiya-Kudo c, Hitoshi Shimano d, Toshifumi Ozaki a a Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences 2-5-1 Shikatacho, kitaku, Okayama 700-8558, Japan b Department of Cellular Differentiation, Institute for Frontier Medical Sciences, Kyoto University 53 Shogoin-Kawaharacho, Sakyoku, Kyoto 606-8507, Japan c Okinaka Memorial Institute for Medical Research, Toranomon Hospital 2-2-2 Toranomon, Minatoku, Tokyo 105-8470, Japan d Department of Internal Medicine, Endocrinology and Metabolism, Advanced Biomedical Applications, Graduate School of Comprehensive Human Sciences Center for Tsukuba Advanced Research Alliance, University of Tsukuba 1-1-1 Tennodai, Tsukuba-city, Ibaraki 305-8575, Japan * Corresponding author at: Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikatacho, Kitaku, Okayama 700-8558, Japan. Tel: +81-86-235-7273; fax: +81-86-223-9727. E-mail address: [email protected] (T. Furumatsu). 1 Abstract During musculoskeletal development, Sry-type HMG box 9 (Sox9) has a crucial role in mesenchymal condensation and chondrogenesis. On the other hand, a tissue-specific basic helix-loop-helix (bHLH) transcription factor Scleraxis (Scx) regulates the differentiation of tendon and ligament progenitors. Whereas these two transcription factors cooperatively participate in the determination of cellular lineages, the precise interaction between Sox9 and Scx remains unclear. We have previously demonstrated that the Sox9-dependent transcription is synergistically activated by several Sox9- associating molecules, such as p300 and Smad3, on chromatin.