And-1 is required for the stability of histone acetyltransferase Gcn5.
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.
Mesh Terms:
Acetylation, Cell Cycle, Cell Line, Cell Line, Tumor, Chromatin Immunoprecipitation, DNA-Binding Proteins, HCT116 Cells, HEK293 Cells, HeLa Cells, Histones, Humans, Immunoblotting, Lysine, Neoplasms, Protein Binding, Protein Stability, RNA Interference, p300-CBP Transcription Factors
Acetylation, Cell Cycle, Cell Line, Cell Line, Tumor, Chromatin Immunoprecipitation, DNA-Binding Proteins, HCT116 Cells, HEK293 Cells, HeLa Cells, Histones, Humans, Immunoblotting, Lysine, Neoplasms, Protein Binding, Protein Stability, RNA Interference, p300-CBP Transcription Factors
Oncogene
Date: Feb. 02, 2012
PubMed ID: 21725360
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