Distinct roles of the Gcn5 histone acetyltransferase revealed during transient stress-induced reprogramming of the genome.

BACKGROUND

Gcn5 belongs to a family of histone acetyltransferases (HATs) that regulate protein function by acetylation. Gcn5 plays several different roles in gene transcription throughout the genome but their characterisation by classical mutation approaches is hampered by the high degree of apparent functional redundancy between HAT proteins.

RESULTS

Here we utilise the reduced redundancy associated with the transiently high levels of genomic reprogramming during stress adaptation as a complementary approach to understand the functions of redundant protein families like HATs. We show genome-wide evidence for two functionally distinct roles of Gcn5. First, Gcn5 transiently re-localises to the ORFs of long genes during stress adaptation. Taken together with earlier mechanistic studies, our data suggests that Gcn5 plays a genome- wide role in specifically increasing the transcriptional elongation of long genes, thus increasing the production efficiency of complete long transcripts. Second, we suggest that Gcn5 transiently interacts with histones close to the transcription start site of the many genes that it activates during stress adaptation by acetylation of histone H3K18, leading to histone depletion, probably as a result of nucleosome loss as has been described previously.

CONCLUSIONS

We show that stress adaptation can be used to elucidate the functions of otherwise redundant proteins, like Gcn5, in gene transcription. Further, we show that normalization of chromatin-associated protein levels in ChIP experiments in relation to the histone levels may provide a useful complement to standard approaches. In the present study analysis of data in this way provides an alternative explanation for previously indicated repressive role of Gcn5 in gene transcription.