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Status |
Public on Jan 07, 2013 |
Title |
Genome-wide mapping of FOXM1 binding reveals co-binding with oestrogen receptor alpha in breast cancer cells (ChIP-seq) |
Organism |
Homo sapiens |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
The forkhead transcription factor FOXM1 is a key regulator of the cell cycle and is overexpressed in cancer. Increased levels of FOXM1 are associated with both poor prognosis and oestrogen receptor (ERalpha) status in primary breast cancer. In this study, we map FOXM1 binding genome wide in both ERalpha-positive (MCF-7) and -negative (MDA-MB-231) breast cancer cells. We identify a common set of FOXM1 binding events at cell cycle-regulating genes, but in addition, in MCF-7 cells we find a high level of concordance with ERalpha-binding regions. FOXM1 binding at these co-binding sites is dependent on ERalpha binding, as depletion of ER protein levels reduced FOXM1 binding. FOXM1 interacts directly with both ERalpha co-activator CARM1 and is required for H3 arginine methylation at the ERalpha complex. Inhibition of FOXM1 activity with the ligand thiostrepton resulted in decreased FOXM1 binding at cca. 1400 sites genome wide and reduced expression of genes correlated with poor prognosis in ERalpha-positive tumour samples. These data demonstrate a novel role for the forkhead protein FOXM1 as an ERalpha cofactor and provide insight into the role of FOXM1 in ERalpha-positive breast cancer.
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Overall design |
The FOXM1-binding sites were mapped by ChIP-Seq in MCF-7 and MDA-MB-231 cells. Cells were treated either with thiostrepton, a FOXM1 inhibitor, or with DMSO (as control). Four replicates were performed in MCF7 cells and two replicates in MDA-MB-231 cells.
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Contributor(s) |
Sanders DA, Ross-Innes CS, Beraldi D, Carroll JS, Balsubramanian S |
Citation(s) |
23347430 |
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Submission date |
Sep 10, 2012 |
Last update date |
May 15, 2019 |
Contact name |
Dario Beraldi |
E-mail(s) |
dario.beraldi@cruk.cam.ac.uk
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Organization name |
Cambridge Research Institute
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Street address |
Robinson Way
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City |
Cambridge |
ZIP/Postal code |
CB2 0RE |
Country |
United Kingdom |
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Platforms (2) |
GPL10999 |
Illumina Genome Analyzer IIx (Homo sapiens) |
GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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Samples (14)
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This SubSeries is part of SuperSeries: |
GSE40767 |
Genome-wide mapping of FOXM1 binding reveals co-binding with estrogen receptor alpha in breast cancer cells |
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Relations |
BioProject |
PRJNA174825 |
SRA |
SRP015695 |