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Estrogen Receptor Versatility

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Science Signaling  27 Jul 2010:
Vol. 3, Issue 132, pp. ec225
DOI: 10.1126/scisignal.3132ec225

The estrogen receptor alpha (ERα) is a classical ligand-activated transcription factor with well-known physiological effects on reproduction, bone physiology, and other functions. Vivar et al. explored the gene regulatory activity of estrogen receptor β, a similar molecule with quite distinct antiproliferative and anti-inflammatory biological effects that are less well characterized than those of ERα. In the U2OS human osteosarcoma cell line, the authors used microarray analysis to characterize ERβ-dependent gene expression. Unlike the effects of ERα, which regulated gene expression only when cells were exposed to estrogen, induced expression of ERβ alone, without addition of ligand, regulated hundreds (453) of genes. There were also transcripts that responded only when ERβ bound to ligand, but this was a smaller subset (258 genes). A still smaller subset of genes (83) were regulated by the unbound receptor but showed potentiated effects in the presence of estrogen. Furthermore, analysis of ERβ binding to examples of the three classes of responsive genes showed that differential binding of the receptor is not the main determinant of responsiveness, because ERβ bound to all three classes of genes. Analysis of binding sites adjacent to the ERβ binding sites by chromatin immunoprecipitation and sequencing showed enrichment of distinct transcription factor–binding sites in the three classes of genes. Thus, the authors conclude that unlike ERα, which primarily has a single class of responsive genes, which require ligand-activated receptor for regulation, ERβ has three classes of responsive genes. The distinct regulation of these classes of genes appears to depend on interaction of ERβ with other transcription factors or coactivators.

O. I. Vivar, X. Zhao, E. F. Saunier, C. Griffin, O. S. Mayba, M. Tagliaferri, I. Cohen, T. P. Speed, D. C. Leitman, Estrogen receptor β binds to and regulates three distinct classes of target genes. J. Biol. Chem. 285, 22059–22066 (2010). [Abstract] [Full Text]

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