دورية أكاديمية
أعرض في EDS

Notch-dependent and -independent functions of transcription factor RBPJ.

التفاصيل البيبلوغرافية
العنوان: Notch-dependent and -independent functions of transcription factor RBPJ.
المؤلفون: Friedrich T; Institute of Biochemistry, Justus-Liebig-University Giessen, Friedrichstrasse 24, 35392 Giessen, Germany.; Biomedical Informatics and Systems Medicine, Justus-Liebig-University Giessen, Aulweg 128, 35392 Giessen, Germany., Ferrante F; Institute of Biochemistry, Justus-Liebig-University Giessen, Friedrichstrasse 24, 35392 Giessen, Germany., Pioger L; Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS-UMR 5535, 1919 Route de Mende, 34293 cedex 5, Montpellier, France., Nist A; Genomics Core Facility, Institute of Molecular Oncology, Member of the German Center for Lung Research (DZL), Philipps-University, Hans-Meerwein-Str. 3, 35043 Marburg, Germany., Stiewe T; Genomics Core Facility, Institute of Molecular Oncology, Member of the German Center for Lung Research (DZL), Philipps-University, Hans-Meerwein-Str. 3, 35043 Marburg, Germany., Andrau JC; Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS-UMR 5535, 1919 Route de Mende, 34293 cedex 5, Montpellier, France., Bartkuhn M; Biomedical Informatics and Systems Medicine, Justus-Liebig-University Giessen, Aulweg 128, 35392 Giessen, Germany.; Institute for Lung Health, Aulweg 132, 35392 Giessen, Germany., Giaimo BD; Institute of Biochemistry, Justus-Liebig-University Giessen, Friedrichstrasse 24, 35392 Giessen, Germany., Borggrefe T; Institute of Biochemistry, Justus-Liebig-University Giessen, Friedrichstrasse 24, 35392 Giessen, Germany.
المصدر: Nucleic acids research [Nucleic Acids Res] 2022 Aug 12; Vol. 50 (14), pp. 7925-7937.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE
أسماء مطبوعة: Publication: 1992- : Oxford : Oxford University Press
Original Publication: London, Information Retrieval ltd.
مواضيع طبية MeSH: Immunoglobulin J Recombination Signal Sequence-Binding Protein*/genetics , Immunoglobulin J Recombination Signal Sequence-Binding Protein*/metabolism , Receptors, Notch*/genetics , Receptors, Notch*/metabolism , T-Lymphocytes*/metabolism, Gene Expression Regulation ; Signal Transduction
مستخلص: Signal transduction pathways often involve transcription factors that promote activation of defined target gene sets. The transcription factor RBPJ is the central player in Notch signaling and either forms an activator complex with the Notch intracellular domain (NICD) or a repressor complex with corepressors like KYOT2/FHL1. The balance between these two antagonizing RBPJ-complexes depends on the activation state of the Notch receptor regulated by cell-to-cell interaction, ligand binding and proteolytic cleavage events. Here, we depleted RBPJ in mature T-cells lacking active Notch signaling and performed RNA-Seq, ChIP-Seq and ATAC-seq analyses. RBPJ depletion leads to upregulation of many Notch target genes. Ectopic expression of NICD1 activates several Notch target genes and enhances RBPJ occupancy. Based on gene expression changes and RBPJ occupancy we define four different clusters, either RBPJ- and/or Notch-regulated genes. Importantly, we identify early (Hes1 and Hey1) and late Notch-responsive genes (IL2ra). Similarly, to RBPJ depletion, interfering with transcriptional repression by squelching with cofactor KYOT2/FHL1, leads to upregulation of Notch target genes. Taken together, RBPJ is not only an essential part of the Notch co-activator complex but also functions as a repressor in a Notch-independent manner.
(© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)
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المشرفين على المادة: 0 (Immunoglobulin J Recombination Signal Sequence-Binding Protein)
0 (Receptors, Notch)
تواريخ الأحداث: Date Created: 20220718 Date Completed: 20220815 Latest Revision: 20220914
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC9371899
DOI: 10.1093/nar/gkac601
PMID: 35848919
قاعدة البيانات: MEDLINE
الوصف
تدمد:1362-4962
DOI:10.1093/nar/gkac601