Genome-wide analysis of gene expression regulated by the HAT cofactor Trrap in conditional knockout cells

Transactivation/transformation-domain associated protein (TRRAP) is a component of several multi-protein HAT complexes implicated in both transcriptional regulation and DNA repair. We recently identified Trrap, the murine ortholog of TRRAP, as an essential protein implicated in mitotic progression control, although its target genes are not known. In the present study, we analyzed the expression profiles of Trrap-responsive genes, using cDNA microarray in mitotic cells. From a panel of 17 664 transcript elements, we found that loss of Trrap leads to expression alteration of a large fraction of genes at mitotic stage. Functional classification of these genes indicates that Trrap influences a variety of cellular processes including cell cycle progression, cytoskeleton and cell adhesion, protein turnover, metabolism and signal transduction. The majority (71%) of differentially expressed genes was down-regulated in Trrap- deficient cells, whereas the rest were up-regulated, suggesting that Trrap may also play a role in transcriptional silencing. ChIP analysis revealed that Trrap might regulate gene expression by participating in acetylation of histone H4 and/or H3 depending on target genes and cell cycle stage. Our study indicates that Trrap regulates the expression of a wide range of genes in both quiescence and mitotic stages. Removal of the Trrap protein is associated with both increased and decreased gene expression.