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Multiple transcription factor elements collaborate with estrogen receptor α to activate an inducible estrogen response element in the NKG2E gene

Endocrinology, ISSN: 0013-7227, Vol: 148, Issue: 7, Page: 3449-3450
2007
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Article Description

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 ) and selective estrogen receptor modulators (SERMs). We previously showed that the killer cell lectin-like receptor (NKG2E) gene is regulated by E, tamoxifen, and raloxifene. Here we used the NKG2E gene as a model to investigate the mechanism whereby target genes are regulated by E and SERMs with ERα. 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 β 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 and SERMs was restored when the c-jun, heat-shock factor-2, and CCAAT/enhancer-binding protein β cluster was placed upstream of the variant ERE. The activation of the NKG2E gene by E 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. Copyright © 2007 by The Endocrine Society.

Bibliographic Details

Levy, Nitzan; Zhao, Xiaoyue; Tang, Hui; Jaffe, Robert B; Speed, Terence P; Leitman, Dale C

The Endocrine Society

Biochemistry, Genetics and Molecular Biology

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