GSE23852
Activator protein-2? is a critical determinant of estrogen receptor interactome formation and gene transcription in breast cancer [ChIP-Seq]
Estrogen receptor a (ERa) is key player in the progression of breast cancer. ERa 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 ERa binding sites (ERBS) identified from the recent ChIA-PET of ERa. More importantly, we demonstrate that AP-2? (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 ERa binding events. Furthermore, pertubation of AP-2? expression disrupts ERa DNA binding, long-range chromatin interactions, and gene transcription. Using ChIP-seq, we show that AP-2? and ERa 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-2? 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-2? and FoxA1. Together, our results suggest AP-2? is an essential factor in ERa-mediated transcription, primarily working together with FoxA1 to facilitate ERa binding and long-range chromatin interactions. Overall design: Genome-wide binding analysis of AP-2? and FoxA1 in MCF-7 with and without E2 (estradiol) stimulation using ChIP-Seq.