Electronic Resource
Bcor loss perturbs myeloid differentiation and promotes leukaemogenesis.
| العنوان: | Bcor loss perturbs myeloid differentiation and promotes leukaemogenesis. |
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| المؤلفون: | Kelly M.J., Rogers A.J., Gregory G., Li J., Zethoven M., Gearhart M.D., Bardwell V.J., Johnstone R.W., Vervoort S.J., Kats L.M., So J. |
| بيانات النشر: | Nature Publishing Group (Houndmills, Basingstoke, Hampshire RG21 6XS, United Kingdom) United Kingdom 2019-03-29 |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | The BCL6 Corepressor (BCOR) is a component of a variant Polycomb repressive complex 1 (PRC1) that is essential for normal development. Recurrent mutations in the BCOR gene have been identified in acute myeloid leukaemia and myelodysplastic syndrome among other cancers; however, its function remains poorly understood. Here we examine the role of BCOR in haematopoiesis in vivo using a conditional mouse model that mimics the mutations observed in haematological malignancies. Inactivation of Bcor in haematopoietic stem cells (HSCs) results in expansion of myeloid progenitors and co-operates with oncogenic KrasG12D in the initiation of an aggressive and fully transplantable acute leukaemia. Gene expression analysis and chromatin immunoprecipitation sequencing reveals differential regulation of a subset of PRC1-target genes including HSC-associated transcription factors such as Hoxa7/9. This study provides mechanistic understanding of how BCOR regulates cell fate decisions and how loss of function contributes to the development of leukaemia.Copyright © 2019, The Author(s). |
| مصطلحات الفهرس: | gene deletion, gene expression, gene frequency, gene mutation, gene ontology, genotyping technique, hematologic malignancy, hematopoietic stem cell transplantation, immunophenotyping, immunoprecipitation, leukemogenesis, LoxP site, mouse, myelodysplastic syndrome, nonhuman, open reading frame, perceptive threshold, receptor down regulation, sequence analysis, transcription initiation, ubiquitination, BMI1 protein/ec [Endogenous Compound], CD11b antigen/ec [Endogenous Compound], protein bcl 6/ec [Endogenous Compound], tamoxifen, transcription factor/ec [Endogenous Compound], transcription factor HoxA10/ec [Endogenous Compound], bcor gene, genetic transduction, acute myeloid leukemia, animal cell, animal experiment, animal model, animal tissue, article, blood, bone marrow progenitor cell, cell cloning, cell differentiation, cell proliferation assay, centrifugation, chromatin assembly and disassembly, chromatin immunoprecipitation, chromophore assisted light inactivation, controlled study, CRISPR Cas system, DNA extraction, downstream processing, epigenetic repression, flow cytometry, frameshift mutation, gene, Article |
| URL: | Nature Communications LibKey Link |
| الاتاحة: | Open access content. Open access content Copyright 2019 Elsevier B.V., All rights reserved. |
| Other Numbers: | AUSHL oai:repository.monashhealth.org:1/35719 Nature Communications. 10 (1) (no pagination), 2019. Article Number: 1347. Date of Publication: 01 Dec 2019. 2041-1723 (electronic) https://repository.monashhealth.org/monashhealthjspui/handle/1/35719 30902969 [http://www.ncbi.nlm.nih.gov/pubmed/?term=30902969] 626852812 (Kelly, So, Rogers, Gregory, Li, Zethoven, Johnstone, Vervoort, Kats) The Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia (Kelly, Gregory, Johnstone, Kats) The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3052, Australia (Gregory) Monash Haematology, Monash Health and School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3168, Australia (Gearhart, Bardwell) Department of Genetics, Cell Biology and Development and the Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, United States Kats L.M.; lev.kats@petermac.org 1305115281 |
| المصدر المساهم: | MONASH HEALTH LIBRS From OAIster®, provided by the OCLC Cooperative. |
| رقم الانضمام: | edsoai.on1305115281 |
| قاعدة البيانات: | OAIster |
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