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

Phillippa C Oakford, Sally R James, Abeer Qadi, Alison C West, Shannon N Ray, Andrew G Bert, Peter N Cockerill, Adele F Holloway

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1203-13
Number of pages11
JournalLeukemia Research
Volume34
Issue number9
DOIs
Publication statusPublished - Sep 2010

Bibliographical note

Copyright 2010 Elsevier Ltd. All rights reserved.

Keywords

  • Base Sequence
  • Cell Line
  • Chromatin Immunoprecipitation
  • Core Binding Factor Alpha 2 Subunit
  • DNA Primers
  • Epigenesis, Genetic
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Humans
  • Promoter Regions, Genetic
  • RNA, Small Interfering
  • Transcription, Genetic

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