Multiple transcription factor elements collaborate with estrogen receptor alpha to activate an inducible estrogen response element in the NKG2E gene
- Details
- Publication Year 2007-07,Volume 148,Issue #7,Page 3449-3458
- Journal Title
- ENDOCRINOLOGY
- Publication Type
- Journal Article
- Abstract
- Estrogen receptors (ERs) regulate transcription by interacting with regulatory elements in target genes. However, known ER regulatory elements cannot explain the expression profiles of genes activated by estradiol (E-2) and selective estrogen receptor modulators ( SERMs). We previously showed that the killer cell lectin-like receptor (NKG2E) gene is regulated by E-2, tamoxifen, and raloxifene. Here we used the NKG2E gene as a model to investigate the mechanism whereby target genes are regulated by E-2 and SERMs with ER alpha. The ER regulatory element in the NKG2E promoter was mapped to the - 1825 and - 1686 region. Full activation of the NKG2E promoter required the collaboration between a transcription factor cluster containing c-jun, heat-shock factor 2, and CCAAT/ enhancer-binding protein beta and a unique variant estrogen response element ERE) that has only a two nucleotide spacer between half sites. The cluster elements and the variant ERE were inactive on their own, but the regulation by E-2 and SERMs was restored when the c-jun, heat-shock factor-2, and CCAAT/enhancer-binding protein beta cluster was placed upstream of the variant ERE. The activation of the NKG2E gene by E-2 and selective ER modulators was associated with the recruitment of the p160 coactivators glucocorticoid receptor-interacting protein 1 and amplified in breast cancer 1 but not steroid receptor coactivator 1. These studies identified one of the most complex ER regulatory units thus far reported and demonstrate that a cluster of flanking transcription factors collaborate with ER to induce a functional ERE in the NKG2E promoter.
- Publisher
- ENDOCRINE SOC
- Keywords
- BREAST-CANCER CELLS; NUCLEAR RECEPTORS; TISSUE-SPECIFICITY; BETA-ISOFORM; ER-ALPHA; LIGAND; BINDING; RECRUITMENT; EXPRESSION; TAMOXIFEN
- Publisher's Version
- https://doi.org/10.1210/en.2006-1632
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2007-07-01 12:00:00