Figure 7.
Altered gene expression in VP16–CREBhigh mice. A, Main cellular processes, as defined in gene ontology (GO), affected early (1 week) or late (>3 weeks) after transgene induction. We compared those groups that represent at least a 5% of significantly altered genes either early or late after expression. The main cellular process groups among the 84 probe sets significantly altered during the first week after dox removal included transport, transcription regulation, signal transduction, and synaptic transmission. However, the main GO groups represented in the 161 probe sets significantly altered at late times were related to defense and inflammatory responses, apoptosis, and proteolysis. B, Pathway created with the 161 probe sets significantly altered at late times using Pathways Studio 5.0 software; only direct interactions were considered and unlinked entities were excluded. CREB is labeled in yellow, whereas genes related to pathological response are highlighted in red (red intensities reflect the overlapping of pathology-related groups). Note that most red nodes are not directly connected to CREB. The comparison of this pathway with the pathway obtained for early changes (data not shown) revealed a reduced connectivity with CREB (CREB participates in 48% of early interactions but only in 17% of late interactions) and a much larger presence of genes related with pathological situations (for additional information, see supplemental Fig. S1, available at www.jneurosci.org as supplemental material).