التفاصيل البيبلوغرافية
| العنوان: |
Identification of a Dynamic Core Transcriptional Network in t(8;21) AML that Regulates Differentiation Block and Self-Renewal |
| المؤلفون: |
Ptasinska A, Assi SA, Martinez-Soria N, Imperato MR, Piper J, Cauchy P, Pickin A, James SR, Hoogenkamp M, Williamson D, Wu MC, Tenen DG, Ott S, Westhead DR, Cockerill PN, Heidenreich O, Bonifer C |
| المصدر: |
Cell Reports |
| بيانات النشر: |
Elsevier |
| المجموعة: |
Newcastle University Library ePrints Service |
| الوصف: |
Oncogenic transcription factors such as RUNX1/ETO, which is generated by the chromosomal translocation t(8;21), subvert normal blood cell development by impairing differentiation and driving malignant self-renewal. Here, we use digital foot-printing and chromatin immunoprecipitation sequencing (ChIP-seq) to identify the core RUNX1/ETO- responsive transcriptional network of t(8;21) cells. We show that the transcriptional program underlying leukemic propagation is regulated by a dynamic equilibrium between RUNX1/ETO and RUNX1 complexes, which bind to identical DNA sites in a mutually exclusive fashion. Perturbation of this equilibrium in t(8;21) cells by RUNX1/ETO depletion leads to a global redistribution of transcription factor complexes within preexisting open chromatin, resulting in the formation of a transcriptional network that drives myeloid differentiation. Our work demonstrates on a genome-wide level that the extent of impaired myeloid differentiation in t(8;21) is controlled by the dynamic balance between RUNX1/ETO and RUNX1 activities through the repression of transcription factors that drive differentiation. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
unknown |
| Relation: |
https://eprints.ncl.ac.uk/209764; https://eprints.ncl.ac.uk/fulltext.aspx?url=209764/817D7BC5-88D7-42C9-88E8-5D96850711F8.pdf&pub_id=209764 |
| الاتاحة: |
https://eprints.ncl.ac.uk/209764 |
| Rights: |
https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| رقم الانضمام: |
edsbas.700AD4F5 |
| قاعدة البيانات: |
BASE |