The study presents a comprehensive map of the human chromatin interactome bound by estrogen receptor alpha (ERα) using a novel method called Chromatin Interaction Analysis by Paired-End Tag sequencing (ChIA-PET). This method allows for the identification of long-range chromatin interactions that are critical for transcriptional regulation. The research team developed ChIA-PET to detect global chromatin interactions and mapped the ERα-bound chromatin interactome in estrogen-treated human breast adenocarcinoma cells (MCF-7). They identified 1,451 intrachromosomal and 15 interchromosomal overlapping clusters of chromatin interactions, which suggest that ERα functions by extensive chromatin looping to bring genes together for coordinated transcriptional regulation. The study also shows that most ERα-bound chromatin interactions are functionally involved in regulating specific genes. The results indicate that ERα primarily functions through intrachromosomal mechanisms, and that chromatin interactions are a primary mechanism for regulating transcription in mammalian genomes. The study also demonstrates that ERα-bound chromatin interactions are oestrogen-dependent and that some interactions are false positives. The data suggest that ERα-bound chromatin interactions may regulate gene expression by tethering chromatin interactions, and that these interactions are involved in the regulation of genes involved in various biological processes. The study provides a detailed analysis of the relationship between ERα-bound chromatin interactions and gene expression, and highlights the importance of chromatin interactions in transcriptional regulation. The results demonstrate that the ChIA-PET method is highly reliable and that ERα functions primarily via intrachromosomal mechanisms. The study also shows that high-enrichment ERαBS are more likely to be involved in chromatin interactions than weaker ERαBS. The findings contribute to our understanding of how ERα regulates gene expression through chromatin interactions.The study presents a comprehensive map of the human chromatin interactome bound by estrogen receptor alpha (ERα) using a novel method called Chromatin Interaction Analysis by Paired-End Tag sequencing (ChIA-PET). This method allows for the identification of long-range chromatin interactions that are critical for transcriptional regulation. The research team developed ChIA-PET to detect global chromatin interactions and mapped the ERα-bound chromatin interactome in estrogen-treated human breast adenocarcinoma cells (MCF-7). They identified 1,451 intrachromosomal and 15 interchromosomal overlapping clusters of chromatin interactions, which suggest that ERα functions by extensive chromatin looping to bring genes together for coordinated transcriptional regulation. The study also shows that most ERα-bound chromatin interactions are functionally involved in regulating specific genes. The results indicate that ERα primarily functions through intrachromosomal mechanisms, and that chromatin interactions are a primary mechanism for regulating transcription in mammalian genomes. The study also demonstrates that ERα-bound chromatin interactions are oestrogen-dependent and that some interactions are false positives. The data suggest that ERα-bound chromatin interactions may regulate gene expression by tethering chromatin interactions, and that these interactions are involved in the regulation of genes involved in various biological processes. The study provides a detailed analysis of the relationship between ERα-bound chromatin interactions and gene expression, and highlights the importance of chromatin interactions in transcriptional regulation. The results demonstrate that the ChIA-PET method is highly reliable and that ERα functions primarily via intrachromosomal mechanisms. The study also shows that high-enrichment ERαBS are more likely to be involved in chromatin interactions than weaker ERαBS. The findings contribute to our understanding of how ERα regulates gene expression through chromatin interactions.