دورية أكاديمية
أعرض في EDS

An intricate regulatory circuit between FLI1 and GATA1/GATA2/LDB1/ERG dictates erythroid vs. megakaryocytic differentiation.

التفاصيل البيبلوغرافية
العنوان: An intricate regulatory circuit between FLI1 and GATA1/GATA2/LDB1/ERG dictates erythroid vs. megakaryocytic differentiation.
المؤلفون: Wang C; State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou 550014, P.R. China., Hu M; State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou 550014, P.R. China., Yu K; State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou 550014, P.R. China., Liu W; State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou 550014, P.R. China., Hu A; State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou 550014, P.R. China., Kuang Y; State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou 550014, P.R. China., Huang L; State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou 550014, P.R. China., Gajendran B; State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou 550014, P.R. China., Zacksenhaus E; Department of Medicine, University of Toronto, Toronto, Ontario M5S3H2, Canada., Xiao X; State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou 550014, P.R. China., Ben-David Y; State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou 550014, P.R. China.
المصدر: Molecular medicine reports [Mol Med Rep] 2024 Jun; Vol. 29 (6). Date of Electronic Publication: 2024 May 02.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: D. A. Spandidos Country of Publication: Greece NLM ID: 101475259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1791-3004 (Electronic) Linking ISSN: 17912997 NLM ISO Abbreviation: Mol Med Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Athens, Greece : D. A. Spandidos
مواضيع طبية MeSH: Cell Differentiation*/genetics , Erythroid Cells*/metabolism , Erythroid Cells*/cytology , Megakaryocytes*/metabolism , Megakaryocytes*/cytology, Humans ; Cell Line ; GATA1 Transcription Factor/metabolism ; GATA1 Transcription Factor/genetics ; GATA2 Transcription Factor/metabolism ; GATA2 Transcription Factor/genetics ; Gene Expression Regulation ; LIM Domain Proteins/metabolism ; LIM Domain Proteins/genetics ; Proto-Oncogene Protein c-fli-1/metabolism ; Proto-Oncogene Protein c-fli-1/genetics ; Transcriptional Regulator ERG/metabolism ; Transcriptional Regulator ERG/genetics
مستخلص: During hematopoiesis, megakaryocytic erythroid progenitors (MEPs) differentiate into megakaryocytic or erythroid lineages in response to specific transcriptional factors, yet the regulatory mechanism remains to be elucidated. Using the MEP‑like cell line HEL western blotting, RT‑qPCR, lentivirus‑mediated downregulation, flow cytometry as well as chromatin immunoprecipitation (ChIp) assay demonstrated that the E26 transformation‑specific (ETS) transcription factor friend leukemia integration factor 1 (Fli‑1) inhibits erythroid differentiation. The present study using these methods showed that while FLI1‑mediated downregulation of GATA binding protein 1 (GATA1) suppresses erythropoiesis, its direct transcriptional induction of GATA2 promotes megakaryocytic differentiation. GATA1 is also involved in megakaryocytic differentiation through regulation of GATA2. By contrast to FLI1, the ETS member erythroblast transformation‑specific‑related gene ( ERG ) negatively controls GATA2 and its overexpression through exogenous transfection blocks megakaryocytic differentiation. In addition, FLI1 regulates expression of LIM Domain Binding 1 (LDB1) during erythroid and megakaryocytic commitment, whereas shRNA‑mediated depletion of LDB1 downregulates FLI1 and GATA2 but increases GATA1 expression. In agreement, LDB1 ablation using shRNA lentivirus expression blocks megakaryocytic differentiation and modestly suppresses erythroid maturation. These results suggested that a certain threshold level of LDB1 expression enables FLI1 to block erythroid differentiation. Overall, FLI1 controlled the commitment of MEP to either erythroid or megakaryocytic lineage through an intricate regulation of GATA1/GATA2, LDB1 and ERG, exposing multiple targets for cell fate commitment and therapeutic intervention.
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فهرسة مساهمة: Keywords: GATA binding protein 2; GATA binding protein 1; LIM Domain Binding 1; erythroblast transformation‑specific‑related gene; erythroid differentiation/megakaryocytic differentiation; friend leukemia integration factor 1; transcriptional regulation
المشرفين على المادة: 0 (ERG protein, human)
0 (FLI1 protein, human)
0 (GATA1 protein, human)
0 (GATA2 protein, human)
تواريخ الأحداث: Date Created: 20240502 Date Completed: 20240502 Latest Revision: 20240520
رمز التحديث: 20240520
مُعرف محوري في PubMed: PMC11082641
DOI: 10.3892/mmr.2024.13231
PMID: 38695236
قاعدة البيانات: MEDLINE
الوصف
تدمد:1791-3004
DOI:10.3892/mmr.2024.13231