ETO2-GLIS2 Hijacks Transcriptional Complexes to Drive Cellular Identity and Self-Renewal in Pediatric Acute Megakaryoblastic Leukemia
Details
Publication Year 2017-03-13, Volume 31, Issue #3, Page 452-465
Journal Title
Cancer Cell
Publication Type
Journal Article
Abstract
Chimeric transcription factors are a hallmark of human leukemia, but the molecular mechanisms by which they block differentiation and promote aberrant self-renewal remain unclear. Here, we demonstrate that the ETO2-GLIS2 fusion oncoprotein, which is found in aggressive acute megakaryoblastic leukemia, confers megakaryocytic identity via the GLIS2 moiety while both ETO2 and GLIS2 domains are required to drive increased self-renewal properties. ETO2-GLIS2 directly binds DNA to control transcription of associated genes by upregulation of expression and interaction with the ETS-related ERG protein at enhancer elements. Importantly, specific interference with ETO2-GLIS2 oligomerization reverses the transcriptional activation at enhancers and promotes megakaryocytic differentiation, providing a relevant interface to target in this poor-prognosis pediatric leukemia.
Publisher
Cell Press
WEHI Research Division(s)
Chemical Biology
PubMed ID
28292442
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2017-04-12 10:42:25
Last Modified: 2017-04-12 11:47:19
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