دورية أكاديمية
Identification of singles bar as a direct transcriptional target of Drosophila Myocyte enhancer factor-2 and a regulator of adult myoblast fusion.
العنوان: | Identification of singles bar as a direct transcriptional target of Drosophila Myocyte enhancer factor-2 and a regulator of adult myoblast fusion. |
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المؤلفون: | Brunetti TM; Department of Biology, University of New Mexico, Albuquerque, NM 87131, USA., Fremin BJ; Department of Biology, University of New Mexico, Albuquerque, NM 87131, USA., Cripps RM; Department of Biology, University of New Mexico, Albuquerque, NM 87131, USA. Electronic address: rcripps@unm.edu. |
المصدر: | Developmental biology [Dev Biol] 2015 May 15; Vol. 401 (2), pp. 299-309. Date of Electronic Publication: 2015 Mar 19. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 0372762 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-564X (Electronic) Linking ISSN: 00121606 NLM ISO Abbreviation: Dev Biol Subsets: MEDLINE |
أسماء مطبوعة: | Publication: San Diego, CA : Elsevier Original Publication: New York. |
مواضيع طبية MeSH: | Drosophila/*embryology , Drosophila Proteins/*genetics , Membrane Proteins/*genetics , Myoblasts/*cytology , Myogenic Regulatory Factors/*genetics , Transcriptional Activation/*genetics, Animals ; Animals, Genetically Modified ; Base Sequence ; Binding Sites/genetics ; Cell Fusion ; Cell Nucleus/genetics ; Chromatin Immunoprecipitation ; DNA-Binding Proteins/biosynthesis ; DNA-Binding Proteins/genetics ; Electrophoretic Mobility Shift Assay ; Gene Expression Regulation, Developmental ; Giant Cells/cytology ; MARVEL Domain-Containing Proteins/biosynthesis ; MARVEL Domain-Containing Proteins/genetics ; Molecular Sequence Data ; Muscle Development/genetics ; Muscle Fibers, Skeletal ; RNA Interference ; RNA, Small Interfering |
مستخلص: | In Drosophila, myoblast fusion is a conserved process in which founder cells (FCs) and fusion competent myoblasts (FCMs) fuse to form a syncytial muscle fiber. Mutants for the myogenic regulator Myocyte enhancer factor-2 (MEF2) show a failure of myoblast fusion, indicating that MEF2 regulates the fusion process. Indeed, chromatin immunoprecipitation studies show that several genes involved in myoblast fusion are bound by MEF2 during embryogenesis. Of these, the MARVEL domain gene singles bar (sing), is down-regulated in MEF2 knockdown pupae, and has five consensus MEF2 binding sites within a 9000-bp region. To determine if MEF2 is an essential and direct regulator of sing during pupal muscle development, we identified a 315-bp myoblast enhancer of sing. This enhancer was active during myoblast fusion, and mutation of two MEF2 sites significantly decreased enhancer activity. We show that lack of sing expression resulted in adult lethality and muscle loss, due to a failure of fusion during the pupal stage. Additionally, we sought to determine if sing was required in either FCs or FCMs to support fusion. Interestingly, knockdown of sing in either population did not significantly affect fusion, however, knockdown in both FCs and FCMs resulted in muscles with significantly reduced nuclei numbers, provisionally indicating that sing function is required in either cell type, but not both. Finally, we found that MEF2 regulated sing expression at the embryonic stage through the same 315-bp enhancer, indicating that sing is a MEF2 target at both critical stages of myoblast fusion. Our studies define for the first time how MEF2 directly controls fusion at multiple stages of the life cycle, and provide further evidence that the mechanisms of fusion characterized in Drosophila embryos is also used in the formation of the more complex adult muscles. (Copyright © 2015 Elsevier Inc. All rights reserved.) |
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معلومات مُعتمدة: | P30 GM110907 United States GM NIGMS NIH HHS; P20 GM103452 United States GM NIGMS NIH HHS; R25 GM060201 United States GM NIGMS NIH HHS; R01 GM061738 United States GM NIGMS NIH HHS; GM061738 United States GM NIGMS NIH HHS |
فهرسة مساهمة: | Keywords: Drosophila; MARVEL domain; MEF2; Myoblast fusion; Singles bar; Transcriptional regulation |
المشرفين على المادة: | 0 (DNA-Binding Proteins) 0 (Drosophila Proteins) 0 (MARVEL Domain-Containing Proteins) 0 (Mef2 protein, Drosophila) 0 (Membrane Proteins) 0 (Myogenic Regulatory Factors) 0 (RNA, Small Interfering) 0 (sing protein, Drosophila) |
تواريخ الأحداث: | Date Created: 20150324 Date Completed: 20150804 Latest Revision: 20240610 |
رمز التحديث: | 20240610 |
مُعرف محوري في PubMed: | PMC4424145 |
DOI: | 10.1016/j.ydbio.2015.02.026 |
PMID: | 25797154 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1095-564X |
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DOI: | 10.1016/j.ydbio.2015.02.026 |