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And-1 is required for the stability of histone acetyltransferase Gcn5

Oncogene volume 31, pages 643–652 (2012)Cite this article

Abstract

Histone acetyltransferases (HATs) have a central role in the modification of chromatin as well as in the pathogenesis of a broad set of diseases including cancers. Gcn5 is the first identified transcription-related HAT that has been implicated in the regulation of diverse cellular functions. However, how Gcn5 proteins are regulated remains largely unknown. Here we show that acidic nucleoplasmic DNA-binding protein (And-1, a high mobility group domain-containing protein) has remarkable capability to regulate the stability of Gcn5 proteins and thereby histone H3 acetylation. We find that And-1 forms a complex with both histone H3 and Gcn5. Downregulation of And-1 results in Gcn5 degradation, leading to the reduction of H3K9 and H3K56 acetylation. And-1 overexpression stabilizes Gcn5 through protein-protein interactions in vivo. Furthermore, And-1 expression is increased in cancer cells in a manner correlating with increased Gcn5 and H3K9Ac and H3K56Ac. Thus, our data reveal not only a functional link between Gcn5 and And-1 that is essential for Gcn5 protein stability and histone H3 acetylation, but also a potential role of And-1 in cancer.

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Acknowledgements

We thank Anindya Dutta for And-1 plasmids and antibodies, Ezra Burstein for Gcn5 plasmids, Rakesh Kumar and Jeyanthy Eswaran for reading the manuscript. This work was supported by funding from the National Institutes of Health (4R00CA136555 awarded to WZ; CA120316 awarded to NHL).

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, The George Washington University Medical School, Washington, DC, USA

    Y Li, A N Jaramillo-Lambert, Y Yang & W Zhu

  2. Department of Pharmacology & Physiology, The George Washington University Medical School, Washington, DC, USA

    R Williams & N H Lee

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  1. Y Li
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Correspondence to W Zhu.

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Li, Y., Jaramillo-Lambert, A., Yang, Y. et al. And-1 is required for the stability of histone acetyltransferase Gcn5. Oncogene 31, 643–652 (2012). https://doi.org/10.1038/onc.2011.261

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