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

作者：Li Y; Jaramillo Lambert A N; Yang Y; Williams R; Lee N H; Zhu W^*

来源：Oncogene, 2012, 31(5): 643-652.

DOI：10.1038/onc.2011.261

• Ctf4/And-1
• Gcn5
• DNA replication
• histone acetylation

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. Oncogene (2012) 31, 643-652; doi:10.1038/onc.2011.261; published online 4 July 2011

• 出版日期2012-2