دورية أكاديمية
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A lncRNA identifies Irf8 enhancer element in negative feedback control of dendritic cell differentiation.

التفاصيل البيبلوغرافية
العنوان: A lncRNA identifies Irf8 enhancer element in negative feedback control of dendritic cell differentiation.
المؤلفون: Xu H; Department of Cell Biology, Institute of Biomedical Engineering, RWTH Aachen University Medical School, Aachen, Germany.; Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany., Li Z; Institute for Computational Genomics, RWTH Aachen University Medical School, Aachen, Germany., Kuo CC; Institute for Computational Genomics, RWTH Aachen University Medical School, Aachen, Germany., Götz K; Department of Cell Biology, Institute of Biomedical Engineering, RWTH Aachen University Medical School, Aachen, Germany.; Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany., Look T; Department of Cell Biology, Institute of Biomedical Engineering, RWTH Aachen University Medical School, Aachen, Germany.; Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany., de Toledo MAS; Department of Cell Biology, Institute of Biomedical Engineering, RWTH Aachen University Medical School, Aachen, Germany.; Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany.; Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Aachen, Germany., Seré K; Department of Cell Biology, Institute of Biomedical Engineering, RWTH Aachen University Medical School, Aachen, Germany.; Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany., Costa IG; Institute for Computational Genomics, RWTH Aachen University Medical School, Aachen, Germany., Zenke M; Department of Cell Biology, Institute of Biomedical Engineering, RWTH Aachen University Medical School, Aachen, Germany.; Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany.; Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Aachen, Germany.
المصدر: ELife [Elife] 2023 Mar 14; Vol. 12. Date of Electronic Publication: 2023 Mar 14.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012-
مواضيع طبية MeSH: RNA, Long Noncoding*/genetics , RNA, Long Noncoding*/metabolism, Mice ; Animals ; Feedback ; Interferon Regulatory Factors/metabolism ; Cell Differentiation/physiology ; Enhancer Elements, Genetic ; Dendritic Cells
مستخلص: Transcription factors play a determining role in lineage commitment and cell differentiation. Interferon regulatory factor 8 (IRF8) is a lineage determining transcription factor in hematopoiesis and master regulator of dendritic cells (DC), an important immune cell for immunity and tolerance. IRF8 is prominently upregulated in DC development by autoactivation and controls both DC differentiation and function. However, it is unclear how Irf8 autoactivation is controlled and eventually limited. Here, we identified a novel long non-coding RNA transcribed from the +32 kb enhancer downstream of Irf8 transcription start site and expressed specifically in mouse plasmacytoid DC (pDC), referred to as lncIrf8 . The lncIrf8 locus interacts with the lrf8 promoter and shows differential epigenetic signatures in pDC versus classical DC type 1 (cDC1). Interestingly, a sequence element of the lncIrf8 promoter, but not lncIrf8 itself, is crucial for mouse pDC and cDC1 differentiation, and this sequence element confers feedback inhibition of Irf8 expression. Taken together, in DC development Irf8 autoactivation is first initiated by flanking enhancers and then second controlled by feedback inhibition through the lncIrf8 promoter element in the +32 kb enhancer. Our work reveals a previously unrecognized negative feedback loop of Irf8 that orchestrates its own expression and thereby controls DC differentiation.
Competing Interests: HX, ZL, CK, KG, TL, Md, KS, IC, MZ No competing interests declared
(© 2023, Xu et al.)
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فهرسة مساهمة: Keywords: CRISPR; dendritic cell; enhancer; feedback loop; immunology; inflammation; interferon regulatory factor 8; lncRNA; mouse
سلسلة جزيئية: GEO GSE198651; GSE118221; GSE36099; GSE73143; GSE57563; GSE64767; GSE114313; GSE188992
المشرفين على المادة: 0 (interferon regulatory factor-8)
0 (RNA, Long Noncoding)
0 (Interferon Regulatory Factors)
تواريخ الأحداث: Date Created: 20230314 Date Completed: 20230329 Latest Revision: 20230405
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC10042546
DOI: 10.7554/eLife.83342
PMID: 36916882
قاعدة البيانات: MEDLINE
الوصف
تدمد:2050-084X
DOI:10.7554/eLife.83342