Histone deacetylase 1 inactivation by an adenovirus early gene product

Gam1 is an early gene product of the avian adenovirus CELO and is essential for viral replication [1]. Gam1 has no homology to any known proteins; however, its early expression and nuclear localization suggest that the protein functions to influence transcription in the infected cell. A determinant of eukaryotic gene expression is the acetylation state of chromosomal histones and other nuclear proteins [2]. We find that Gam1 expression increases the level of transcription from a variety of eukaryotic promoters, similar to the effect of treating cells with the histone deacetylase (HDAC) inhibitor trichostatin A (TSA [3]). We show that Gam1 can effectively inhibit histone deacetylation by HDAC1 and that Gam1 binds to HDAC1 both in vitro and in vivo. A CELO virus lacking Gam1 (CELOdG) is replication defective [1], but the defect can be overcome by either expressing an interfering HDAC1 mutant or by treating infected cells with TSA. The identification of a viral early gene product having the specific function of binding and inactivating HDAC suggests that deacetylase complexes play an important role in limiting early gene expression from invading viruses.