دورية أكاديمية
Epigenetic regulation of NFE2 overexpression in myeloproliferative neoplasms.
| العنوان: | Epigenetic regulation of NFE2 overexpression in myeloproliferative neoplasms. |
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| المؤلفون: | Peeken JC; Division of Molecular Hematology., Jutzi JS; Division of Molecular Hematology.; Spemann Graduate School of Biology and Medicine (SGBM).; Faculty of Biology, and., Wehrle J; Division of Molecular Hematology.; Berta Ottenstein Program, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; German Cancer Consortium (DKTK), Freiburg, Germany.; German Cancer Research Center (DKFZ), Heidelberg, Germany., Koellerer C; Division of Molecular Hematology., Staehle HF; Division of Molecular Hematology., Becker H; Division of Molecular Hematology., Schoenwandt E; Division of Molecular Hematology., Seeger TS; Division of Molecular Hematology., Schanne DH; Division of Molecular Hematology., Gothwal M; Division of Molecular Hematology., Ott CJ; Center for Cancer Research, Massachusetts General Hospital, Boston, MA; and.; Department of Medicine, Harvard Medical School, Charlestown, MA., Gründer A; Division of Molecular Hematology., Pahl HL; Division of Molecular Hematology.; Spemann Graduate School of Biology and Medicine (SGBM). |
| المصدر: | Blood [Blood] 2018 May 03; Vol. 131 (18), pp. 2065-2073. Date of Electronic Publication: 2018 Mar 08. |
| 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: 7603509 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1528-0020 (Electronic) Linking ISSN: 00064971 NLM ISO Abbreviation: Blood Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York] : Elsevier Original Publication: New York, Grune & Stratton [etc.] |
| مواضيع طبية MeSH: | Epigenesis, Genetic* , Gene Expression* , Gene Expression Regulation*, Myeloproliferative Disorders/*genetics , NF-E2 Transcription Factor, p45 Subunit/*genetics, Biomarkers ; Chromobox Protein Homolog 5 ; Cytokines/metabolism ; DNA Methylation ; Decitabine/pharmacology ; Histones/metabolism ; Humans ; Janus Kinase 2/genetics ; Janus Kinase 2/metabolism ; Jumonji Domain-Containing Histone Demethylases/genetics ; Models, Biological ; Mutation ; Myeloproliferative Disorders/metabolism ; NF-E2 Transcription Factor, p45 Subunit/metabolism ; Oxidoreductases, N-Demethylating/genetics ; Phosphorylation ; Polycythemia Vera/genetics ; Promoter Regions, Genetic ; Protein Binding |
| مستخلص: | The transcription factor "nuclear factor erythroid 2" (NFE2) is overexpressed in the majority of patients with myeloproliferative neoplasms (MPNs). In murine models, elevated NFE2 levels cause an MPN phenotype with spontaneous leukemic transformation. However, both the molecular mechanisms leading to NFE2 overexpression and its downstream targets remain incompletely understood. Here, we show that the histone demethylase JMJD1C constitutes a novel NFE2 target gene. JMJD1C levels are significantly elevated in polycythemia vera (PV) and primary myelofibrosis patients; concomitantly, global H3K9me1 and H3K9me2 levels are significantly decreased. JMJD1C binding to the NFE2 promoter is increased in PV patients, decreasing both H3K9me2 levels and binding of the repressive heterochromatin protein-1α (HP1α). Hence, JMJD1C and NFE2 participate in a novel autoregulatory loop. Depleting JMJD1C expression significantly reduced cytokine-independent growth of an MPN cell line. Independently, NFE2 is regulated through the epigenetic JAK2 pathway by phosphorylation of H3Y41. This likewise inhibits HP1α binding. Treatment with decitabine lowered H3Y41ph and augmented H3K9me2 levels at the NFE2 locus in HEL cells, thereby increasing HP1α binding, which normalized NFE2 expression selectively in JAK2 V617F -positive cell lines. (© 2018 by The American Society of Hematology.) |
| التعليقات: | Comment in: Blood. 2018 May 3;131(18):1998-1999. doi: 10.1182/blood-2018-03-839779. (PMID: 29724716) |
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| معلومات مُعتمدة: | P01 CA108671 United States CA NCI NIH HHS; P50 CA206963 United States CA NCI NIH HHS |
| المشرفين على المادة: | 0 (Biomarkers) 0 (CBX5 protein, human) 0 (Cytokines) 0 (Histones) 0 (NF-E2 Transcription Factor, p45 Subunit) 0 (NFE2 protein, human) 107283-02-3 (Chromobox Protein Homolog 5) 776B62CQ27 (Decitabine) EC 1.14.11.- (JMJD1C protein, human) EC 1.14.11.- (Jumonji Domain-Containing Histone Demethylases) EC 1.5.- (Oxidoreductases, N-Demethylating) EC 2.7.10.2 (JAK2 protein, human) EC 2.7.10.2 (Janus Kinase 2) |
| تواريخ الأحداث: | Date Created: 20180310 Date Completed: 20190521 Latest Revision: 20240922 |
| رمز التحديث: | 20240922 |
| مُعرف محوري في PubMed: | PMC5934799 |
| DOI: | 10.1182/blood-2017-10-810622 |
| PMID: | 29519804 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1528-0020 |
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| DOI: | 10.1182/blood-2017-10-810622 |