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| Status |
Public on Jun 02, 2011 |
| Title |
Activator protein-2γ is a critical determinant of estrogen receptor interactome formation and gene transcription in breast cancer [expression] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Estrogen receptor α (ERα) is key player in the progression of breast cancer. ERα binds to DNA and mediates long-range chromatin interactions throughout the genome, but the underlying mechanism in this process is unclear. Here, we show that AP-2 motifs are highly enriched in the ERα binding sites (ERBS) identified from the recent ChIA-PET of ERα. More importantly, we demonstrate that AP-2γ (also known as TFAP2C), a member of the AP-2 family which has been implicated in breast cancer oncogenesis, is recruited to chromatin in a ligand-independent manner and co-localized with ERα binding events. Furthermore, pertubation of AP-2γ expression disrupts ERα DNA binding, long-range chromatin interactions, and gene transcription. Using ChIP-seq, we show that AP-2γ and ERα binding occurs in close proximity on a genome-wide scale. The majority of these shared genomic regions are also occupied by the pioneer factor, FoxA1. AP-2γ is required for efficient FoxA1 binding and vice versa. Finally, we show that most ERBS associated with long-range chromatin interactions are co-localized with both AP-2γ and FoxA1. Together, our results suggest AP-2γ is an essential factor in ERα-mediated transcription, primarily working together with FoxA1 to facilitate ERα binding and long-range chromatin interactions.
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| Overall design |
Gene expression profiling of negative control (NC) and AP-2γ siRNA transfected MCF-7, with and without E2 (estradiol) stimulation using microarray.
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| Contributor(s) |
Tan SK, Lin Z, Chang CW, Cheung E |
| Citation(s) |
21572391 |
| |
| Submission date |
Jan 20, 2011 |
| Last update date |
Mar 20, 2017 |
| Contact name |
SI KEE TAN |
| E-mail(s) |
tansk99@gis.a-star.edu.sg
|
| Organization name |
Genomic Institute of Singapore
|
| Department |
Cancer biology and Pharmacology
|
| Street address |
60 Biopolis Street #02-01 Genome
|
| City |
Singapore |
| ZIP/Postal code |
Singapore 138672 |
| Country |
Singapore |
| |
|
| Platforms (1) |
| GPL6883 |
Illumina HumanRef-8 v3.0 expression beadchip |
|
| Samples (6)
|
| GSM658197 |
NC-transfected MCF-7, 12h ETOH |
| GSM658198 |
NC-transfected MCF-7, 12h E2 |
| GSM658199 |
siAP-2γ (Dharmacon)-transfected MCF-7, 12h ETOH |
| GSM658200 |
siAP-2γ (Dharmacon)-transfected MCF-7, 12h E2 |
| GSM658201 |
siAP-2γ (First Base)-transfected MCF-7, 12h ETOH |
| GSM658202 |
siAP-2γ (First Base)-transfected MCF-7, 12h E2 |
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| This SubSeries is part of SuperSeries: |
| GSE26741 |
Activator protein-2γ is a critical determinant of estrogen receptor interactome formation and gene transcription in breast cancer |
|
| Relations |
| BioProject |
PRJNA142129 |
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