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Determination of transcription factor binding

Nature Genetics volume 43, pages 11–12 (2011)Cite this article

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To understand transcriptional regulation, it is necessary to understand the factors that determine where a particular transcription factor binds in the genome. A new study demonstrates that a single protein, FoxA1, can dictate the global DNA binding profile and the transcriptional function of estrogen receptor a in breast cancer cells and in other cell types.

Estrogen receptor α (ERα), a member of the nuclear hormone receptor family of transcription factors, is overexpressed in more than two-thirds of individuals with breast cancer and plays an important role in driving the proliferation of breast cancer cells. Tamoxifen, an anti-estrogen drug that binds and inhibits the activity of ERα, has saved or prolonged the lives of hundreds of thousands of breast cancer patients with ERα-positive tumors. However, most patients eventually become resistant to tamoxifen therapy. Thus, understanding how ERα functions in breast cancer cells is vitally important. The genomic landscape of ERα binding sites and the chromatin interactions have been mapped recently in breast cancer cells using high-throughput technologies1,2,3. After estrogen stimulation, ERα binds to thousands of specific genomic locations in breast cancer cells, but the factors that determine where ERα binds remain unclear. Interestingly, the majority of these binding sites are enriched for a sequence motif associated with forkhead protein binding, and the forkhead factor FoxA1 was found to co-localize to nearly half of the ERα binding sites in breast cancer cells4,5. On page 27 of this issue, Jason Carroll and colleagues report that FoxA1 is sufficient to dictate the global binding profile of ERα in breast cancer cells and is also required for regulating the binding of ERα in other cell types in which FoxA1 is co-expressed6.

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Figure 1: The proposed model for the role of FoxA1 in determining ERα-chromatin interactions.

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Authors and Affiliations

  1. Edwin Cheung and Yijun Ruan are at the Genome Institute of Singapore, Singapore.,

    Edwin Cheung & Yijun Ruan

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  1. Edwin Cheung
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  2. Yijun Ruan
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Correspondence to Yijun Ruan.

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The authors declare no competing financial interests.

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Cheung, E., Ruan, Y. Determination of transcription factor binding. Nat Genet 43, 11–12 (2011). https://doi.org/10.1038/ng0111-11

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