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

Histone acetyltransferases (HATs) play a central role in the modification of chromatin as well as in pathogenesis of a broad set of diseases including cancers. Gcn5 is the first identified transcription-related histone acetyltransferase (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 And-1 (a HMG 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 to regulate Gcn5 protein stability and histone H3 acetylation, but also a potential role of And-1 in cancer.