The study developed a novel method called Chromatin Interaction Analysis by Paired-End Tag sequencing (ChIA-PET) to detect global chromatin interactions in the human genome. Using this method, the researchers comprehensively mapped the chromatin interaction network bound by estrogen receptor α (ERα) in human breast adenocarcinoma cells (MCF-7) treated with estrogen. They found that most high-confidence remote ERα binding sites are anchored at gene promoters through long-range chromatin interactions, suggesting that ERα functions by extensive chromatin looping to bring genes together for coordinated transcriptional regulation. The study also proposed that chromatin interactions are a primary mechanism for regulating transcription in mammalian genomes. The ChIA-PET method was validated through various controls and replicate experiments, demonstrating its reliability. The ERα-bound chromatin interactome map identified 689 chromatin interaction regions, with most interactions involving distal ERα binding sites. These interactions were associated with gene transcriptional activation, as evidenced by histone modifications and RNA polymerase II occupancy. The study further explored the functional significance of these interactions, showing that they may coordinate transcriptional regulation for multiple genes involved in the same functional pathways. Finally, the researchers confirmed that ERα-bound chromatin interactions are essential for transcription activation by knocking down ERα protein levels in MCF-7 cells.The study developed a novel method called Chromatin Interaction Analysis by Paired-End Tag sequencing (ChIA-PET) to detect global chromatin interactions in the human genome. Using this method, the researchers comprehensively mapped the chromatin interaction network bound by estrogen receptor α (ERα) in human breast adenocarcinoma cells (MCF-7) treated with estrogen. They found that most high-confidence remote ERα binding sites are anchored at gene promoters through long-range chromatin interactions, suggesting that ERα functions by extensive chromatin looping to bring genes together for coordinated transcriptional regulation. The study also proposed that chromatin interactions are a primary mechanism for regulating transcription in mammalian genomes. The ChIA-PET method was validated through various controls and replicate experiments, demonstrating its reliability. The ERα-bound chromatin interactome map identified 689 chromatin interaction regions, with most interactions involving distal ERα binding sites. These interactions were associated with gene transcriptional activation, as evidenced by histone modifications and RNA polymerase II occupancy. The study further explored the functional significance of these interactions, showing that they may coordinate transcriptional regulation for multiple genes involved in the same functional pathways. Finally, the researchers confirmed that ERα-bound chromatin interactions are essential for transcription activation by knocking down ERα protein levels in MCF-7 cells.