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Transcriptional and epigenetic regulation of the GM-CSF promoter by RUNX1

Citation

Oakford, PC and James, SR and Qadi, A and West, AC and Ray, SN and Bert, AG and Cockerill, PN and Holloway, AF, Transcriptional and epigenetic regulation of the GM-CSF promoter by RUNX1, Leukemia Research, 34, (9) pp. 1203-1213. ISSN 0145-2126 (2010) [Refereed Article]


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DOI: doi:10.1016/j.leukres.2010.03.029

Abstract

The RUNX1 gene, which is essential for normal hematopoiesis, is frequently rearranged by the t(8;21) chromosomal translocation in acute myeloid leukemia. The resulting RUNX1–ETO fusion protein contributes to leukemic progression by directing aberrant association of transcriptional cofactors and epigenetic modifiers to RUNX1 target genes. For example, the GM-CSF gene is activated by RUNX1, but is repressed by RUNX1–ETO. Here we show that RUNX1 normally cooperates with the histone acetyltransferase, CBP, to regulate GM-CSF expression at two levels. Firstly, it directs the establishment of a competent chromatin environment at the GM-CSF promoter prior to gene activation. It then participates in the transcriptional activation of the promoter in response to immune stimuli. In contrast, RUNX1–ETO,which cannot associate with CBP, is unable to transactivate the GM-CSF promoter and is associated with the generation of a repressive chromatin environment at the promoter.

Item Details

Item Type:Refereed Article
Keywords:RUNX1, Transcription, Chromatin, GM-CSF, Oncoprotein
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Epigenetics (incl. Genome Methylation and Epigenomics)
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cancer and Related Disorders
Author:Oakford, PC (Dr Phillippa Taberlay)
Author:Qadi, A (Ms Abeer Qadi)
Author:West, AC (Ms Alison West)
Author:Ray, SN (Mrs Shannon Huskins)
Author:Holloway, AF (Associate Professor Adele Holloway)
ID Code:64988
Year Published:2010
Web of Science® Times Cited:7
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-09-21
Last Modified:2011-05-02
Downloads:0

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