Figure 1.
SARE sequences are found in intergenic and intronic genetic regions.
Scheme showing consensus TFBS for SARE sequence and the SARE sequenced found in the promoter of SOX14 (top). For the SynoR search, random relative position of the three TFBS was permitted. Table shows the number and percentages of SARE sequences classified according to their position within the genes and the diagram represents the distribution of each category.
Table 1.
SARE regulation affects several aspects of neuron function.
Table 2.
Classification of SARE-containing genes at GO indicated significant enrichment of processes related to the nervous system.
Figure 2.
Up-regulation of the mRNA of SARE containing genes and promoter activation in response to neuronal activity. A)
Upregulation of SARE identified candidates in primary cortical neurons. Primary neurons from E18 cortex were cultivated for 16 days before triggering neuronal activation with 4AP/bicuculline. RNA was obtained and transcript expression of SARE containing genes analyzed by quantitative real time RT-PCR (Q-PCR). Expression of each gene is normalized to the expression in control cells. Arc up-regulation demonstrated efficient neuronal activation. * indicates p<0,5 **<0,1, ***<0,05 (t-Student test). B). Novel SARE sequences activate transcription in response to neuronal activity. Mouse genomic sequence containing SARE regulatory regions (see below) corresponding to those identified for the Cux1 and Cux2 genes were cloned into the pGL4.23 luciferase vector (Promega). Neurons obtained from E18,5 cortex were co-transfected with the indicated firefly luciferase reporter construct and internal control Renilla luciferase plasmid at a ratio of 4∶1. Neuronal activity was trigered with 4AP/bicuculline before measuring transcription of the reporters. Relative expression of each reporter constructs was determined by normalizing the activity of each reporter to its activity on TTX treated neurons. Data represent mean and standar deviation of results obtained in three different experiments. * indicates p<0,01, **<0,001 (t-Student test).
Table 3.
The number of SARE containing genes is significantly enriched on genes up-regulated upon bicuculline triggering of neuronal activity.
Table 4.
FMRP targets containing SARE sequence genes.