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ERα condensates: chronic stimulation is hard to ignore

Nature Structural & Molecular Biology volume 26, pages 153–154 (2019)Cite this article

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Last year, several studies reported that proteins form biomolecular condensates at gene enhancers. Nair et al. now show that these condensates undergo physical changes over time, which affects their nuclear localization and the transcriptional output of their target genes.

Cells must adapt to changes in their environment by adjusting their intracellular protein composition in response to extracellular signals. One example of a group of proteins that can directly transform those signals into an altered gene-expression profile is hormone receptors. The estrogen receptor ERα, for instance, is bound by its target hormone 17β-estradiol (E2), which leads to receptor dimerization, nuclear translocation, and induction of target-gene expression. Many of the genes activated by ERα encode molecules important for proliferation and cell survival1. The majority of breast cancer cells co-opt this ERα-dependent mechanism to support tumor growth2. In a recent study, Nair et al. used the breast cancer cell line MCF7 to investigate how ERα activates gene transcription after stimulation by E23. Remarkably, the work suggests that ERα forms phase-separated biomolecular condensates on enhancer target sites that undergo changes in their physical properties with time, which results in reduced enhancer activity and gene expression.

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Fig. 1: Model depicting how enhancer condensates are formed and how they lead to the activation of transcription.

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Authors and Affiliations

  1. Max-Planck Institute for Molecular Cell Biology and Genetics, Dresden, Germany

    Sina Wittmann & Simon Alberti

  2. Biotechnology Center (BIOTEC), Center for Molecular and Cellular Bioengineering (CMCB), Technische Universität Dresden, Dresden, Germany

    Simon Alberti

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  1. Sina Wittmann
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  2. Simon Alberti
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Correspondence to Simon Alberti.

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S.A. is a scientific advisor of Dewpoint Therapeutics.

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Wittmann, S., Alberti, S. ERα condensates: chronic stimulation is hard to ignore. Nat Struct Mol Biol 26, 153–154 (2019). https://doi.org/10.1038/s41594-019-0198-x

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