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| Status |
Public on Aug 15, 2014 |
| Title |
Suppression of the FOXM1 transcriptional program via novel small molecule inhibition |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The transcription factor FOXM1 binds to sequence-specific motifs on DNA (C/TAAACA) through its DNA binding domain (DBD), and activates proliferation- and differentiation-associated genes. Aberrant overexpression of FOXM1 is a key feature in oncogenesis and progression of many human cancers. Herein we identify novel inhibitors of FOXM1 that block DNA binding from a high-throughput screen applied to a library of 54,211 small molecules. One compound, FDI-6 (NCGC00099374) is studied in depth and is shown to bind directly to FOXM1 protein, displace the transcription factor from genomic targets in MCF-7 breast cancer cells, and induce concomitant transcriptional down-regulation. Global transcript profiling of MCF-7 cells by RNA-seq shows that FDI-6 specifically down regulates FOXM1-activated genes with FOXM1 occupancy confirmed by ChIP-seq. This small molecule mediated effect is selective for FOXM1-controlled genes with no effect on genes regulated by homologous forkhead family factors.
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| Overall design |
12 samples, 100 single-ended RNAseq libraries: 3 replicates for untreated (0 hours); 3 replicates for 3 hours treatment; 3 replicates for 6 hours treatment; 3 replicates for 9 hours treatment. Treatment: compound FDI-6 inhibiting binding of FOXM-1 to DNA.
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| Contributor(s) |
Gormally MV, Dexheimer TS, Marsico G, Sanders DA, Lowe C, Matak-Vinković D, Jadhav A, Rai G, Maloney DJ, Simeonov A, Balasubramanian S |
| Citation(s) |
25387393, 26484143 |
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| Submission date |
Jun 18, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Giovanni Marsico |
| E-mail(s) |
persego@gmail.com
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| Organization name |
CRUK Cambridge 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 (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA253038 |
| SRA |
SRP043378 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE58626_RAW.tar |
1.1 Mb |
(http)(custom) |
TAR (of TSV) |
| GSE58626_README.txt |
1.0 Kb |
(ftp)(http) |
TXT |
| GSE58626_detable_all_cluster.tsv.gz |
767.7 Kb |
(ftp)(http) |
TSV |
| GSE58626_genes.htseq.txt.gz |
351.4 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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