| Title | Lactogenic hormonal induction of long-distance interactions between {beta}-casein gene regulatory elements. | | Author(s) | Kabotyanski EB, Rijnkels M, Freeman-Zadrowski C, Buser AC, Edwards DP, Rosen JM | | Institution | Baylor College of Medicine, United States. | | Source | J Biol Chem 2009 Jun 19. | | Abstract | Lactogenic hormone regulation of beta-casein gene expression in mammary epithelial cells provides an excellent model in which to study the mechanisms by which steroid and peptide hormone signaling control gene expression. Prolactin and glucocorticoid mediated induction of beta-casein gene expression involves two principal regulatory regions, a proximal promoter and a distal enhancer located in the mouse approximately -6 kb upstream of the transcription start site. Using a chromosome conformation capture (3C) assay and quantitative real-time PCR, we demonstrate that a chromatin loop is created in conjunction with the recruitment of specific transcription factors and p300 in HC11 mammary epithelial cells. Stimulation with both prolactin and hydrocortisone is required for the induction of these long-range interactions between the promoter and enhancer, and no DNA looping was observed in non-treated cells or cells treated with each of the hormones separately. The lactogenic hormone-induced interaction between the proximal promoter and distal enhancer was confirmed in hormone-treated primary 3D mammary acini cultures. In addition, the developmental regulation of DNA looping between the beta-casein regulatory regions was observed in lactating but not in virgin mouse mammary glands. Furthermore, beta-casein mRNA induction and long-range interactions between these regulatory regions were inhibited in a progestin-dependent manner following stimulation with prolactin and hydrocortisone in HC11 cells expressing human PR-B. Collectively, these data suggest that the communication between these regulatory regions with intervening DNA looping is a crucial step required to both create and maintain active chromatin domains and regulate transcription. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19542223 |
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