Estrogen-mediated epigenetic repression of large chromosomal regions through DNA looping is a study that explores how estrogen signaling influences the epigenetic silencing of large chromosomal regions in breast cells. The research, published in Genome Research, reveals that estrogen can induce the formation of DNA loops that facilitate the coordinated repression of multiple genes. This process is observed in both normal breast epithelial cells and breast cancer cells, but the mechanism differs between the two. In normal cells, estrogen signaling leads to the transient formation of DNA loops that bring distant loci to ESR1 binding sites, enabling coordinate repression. However, in breast cancer cells, this plasticity is reduced, and the establishment of a rigid DNA scaffold may reinforce estrogen-mediated repression. The study used an integrative approach, combining transcriptome, methylome, and estrogen receptor alpha (ESR1)-binding datasets from normal breast epithelia and breast cancer cells. This "omics" approach identified large repressive zones, including a 14-gene cluster on 16p11.2. In normal cells, estrogen signaling induces the formation of DNA loops in this region, bringing distant promoters to ESR1 binding sites for coordinate repression. However, in cancer cells, this transient movement is lost, and the establishment of a permanent loop structure is present in the epigenetically repressed region. The study also found that the 16p11.2 gene cluster is associated with H3K27me3 and DNA hypermethylation in breast cancer cells. These epigenetic marks contribute to the long-term repression of the loci. Additionally, the study demonstrated that estrogen signaling can mediate DNA looping through ESR1 binding sites, which is essential for the coordinated repression of the 14-gene cluster. The findings suggest that estrogen-mediated epigenetic repression is a complex process that involves both DNA looping and epigenetic modifications. The study highlights the importance of understanding these mechanisms in the context of breast cancer development and progression. The research provides insights into the role of estrogen signaling in the epigenetic regulation of gene expression and offers a new perspective on the mechanisms underlying long-range epigenetic silencing in cancer cells.Estrogen-mediated epigenetic repression of large chromosomal regions through DNA looping is a study that explores how estrogen signaling influences the epigenetic silencing of large chromosomal regions in breast cells. The research, published in Genome Research, reveals that estrogen can induce the formation of DNA loops that facilitate the coordinated repression of multiple genes. This process is observed in both normal breast epithelial cells and breast cancer cells, but the mechanism differs between the two. In normal cells, estrogen signaling leads to the transient formation of DNA loops that bring distant loci to ESR1 binding sites, enabling coordinate repression. However, in breast cancer cells, this plasticity is reduced, and the establishment of a rigid DNA scaffold may reinforce estrogen-mediated repression. The study used an integrative approach, combining transcriptome, methylome, and estrogen receptor alpha (ESR1)-binding datasets from normal breast epithelia and breast cancer cells. This "omics" approach identified large repressive zones, including a 14-gene cluster on 16p11.2. In normal cells, estrogen signaling induces the formation of DNA loops in this region, bringing distant promoters to ESR1 binding sites for coordinate repression. However, in cancer cells, this transient movement is lost, and the establishment of a permanent loop structure is present in the epigenetically repressed region. The study also found that the 16p11.2 gene cluster is associated with H3K27me3 and DNA hypermethylation in breast cancer cells. These epigenetic marks contribute to the long-term repression of the loci. Additionally, the study demonstrated that estrogen signaling can mediate DNA looping through ESR1 binding sites, which is essential for the coordinated repression of the 14-gene cluster. The findings suggest that estrogen-mediated epigenetic repression is a complex process that involves both DNA looping and epigenetic modifications. The study highlights the importance of understanding these mechanisms in the context of breast cancer development and progression. The research provides insights into the role of estrogen signaling in the epigenetic regulation of gene expression and offers a new perspective on the mechanisms underlying long-range epigenetic silencing in cancer cells.