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. 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. 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 ). 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, 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.
Chiocca
Susanna
S
Department of Experimental Oncology, European Institute of Oncology, 20141, Milan, Italy. schiocca@ieo.it
Kurtev
Vladislav
V
Colombo
Riccardo
R
Boggio
Roberto
R
Sciurpi
M Teresa
MT
Brosch
Gerald
G
Seiser
Christian
C
Draetta
Giulio F
GF
Cotten
Matt
M
D000818:Animals; D000259:Aviadenovirus / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D015870:Gene Expression; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000235:genetics; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D000099186:Histone Deacetylase 3
D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D006877:Hydroxamic Acids; D017874:Immediate-Early Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014764:Viral Proteins; D000099186:Histone Deacetylase 3; C105052:CELO protein, adenovirus; C012589:trichostatin A; C110550:HDAC1 protein, human