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Transcriptional and epigenetic regulation of the GM-CSF promoter by RUNX1
journal contribution
posted on 2023-05-17, 03:13 authored by Phillippa TaberlayPhillippa Taberlay, James, SR, Qadi, A, West, AC, Shannon HuskinsShannon Huskins, Bert, AG, Cockerill, PN, Adele HollowayAdele HollowayThe 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.
History
Publication title
Leukemia ResearchVolume
34Issue
9Pagination
1203-1213ISSN
0145-2126Department/School
Menzies Institute for Medical ResearchPublisher
Pergamon-Elsevier Science LtdPlace of publication
The Boulevard, Langford Lane, Kidlington, Oxford, England, Ox5 1GbRights statement
The definitive version is available at http://www.sciencedirect.comRepository Status
- Restricted