Estrogen Receptor and Gene Silencing

doi:10.1126/stke.2002.154.tw371

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Sci. STKE, 15 October 2002
Vol. 2002, Issue 154, p. tw371
[DOI: 10.1126/stke.2002.154.tw371]

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TRANSCRIPTION Estrogen Receptor and Gene Silencing

A complex picture is emerging of the many ways by which nuclear receptors for the hormone estrogen regulate gene expression. Estrogen receptors alpha and beta (ER ${alpha}$ and ERß) can act through either a ligand-dependent or -independent mechanism, and receptor activity is further influenced by various coactivators and corepressors. The expression of caveolin-1, a protein best known for its role in caveolae development at the cell surface, is regulated in some tissues by estrogen. Because caveolin-1 can itself bind to ER ${alpha}$ and potentiate gene transcription, the functional relationship between estrogen, ERs, and caveolin in regulating cellular processes is of interest. Zschocke et al. report that in a neuronal cell line, ectopic expression of ER ${alpha}$ inhibited caveolin expression in an estrogen-independent manner. The process involved methylation of specific CpG islands in the caveolin-1 promoter region, a modification that is a hallmark of stable gene silencing. ERß counteracted the effect of ER ${alpha}$ on caveolin expression. Although it remains unclear whether ER ${alpha}$ directly suppresses caveolin expression, the inverse relationship of ER ${alpha}$ and caveolin expression observed in some cancer cell lines may be attributed to this epigenetic effect. Furthermore, exposure of embryonic mice to estrogen resulted in decreased caveolin-1 expression in certain brain regions. The authors propose that persistent down-regulation of caveolin expression by estrogen would not only decrease the availability of this ER coregulator but might also prevent formation of caveolae, thus impairing the integration and transduction of signals from the cell surface.

J. Zschocke, D. Manthey, N. Bayatti, B. van der Burg, S. Goodenough, C. Behl, Estrogen receptor ${alpha}$ -mediated silencing of caveolin gene expression in neuronal cells. J. Biol. Chem. 277, 38772-38780 (2002). [Abstract] [Full Text]

Citation: Estrogen Receptor and Gene Silencing. Sci. STKE 2002, tw371 (2002).

The editors suggest the following Related Resources on Science sites:

VIRTUAL JOURNAL Estrogen Receptor $alpha$ -mediated Silencing of Caveolin Gene Expression in Neuronal Cells: Jürgen Zschocke, Dieter Manthey, Nadhim Bayatti, Bart van der Burg, Sharon Goodenough, and Christian Behl (4 October 2002)
J. Biol. Chem. 277 (41), 38772. [DOI: 10.1074/jbc.M205664200]
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