In the current study, we test the ability of positional clustering to detect known TF-binding sites in a series of increasingly noisy sets of yeast promoters, and found marked improvement in the percentage of correct predictions over Gibbs sampling alone. We also present de novo predictions of TF-binding sites in promoter regions of GABA A receptor subunit genes (GABRs) whose expression is altered (either up-regulated or down-regulated) in an animal model of temporal lobe epilepsy (35) . Positional clustering identified a number of putative cis-regulatory sites, many of which correspond to known binding elements for TFs found in the CNS. Mobility shift assays showed several predicted GABR-binding sequences specifically bind nuclear proteins derived from primary neocortical neurons kept in culture. Furthermore, a particular non-consensus GABR putative regulatory sequence was shown to have a functional role in cultured cortical neurons demonstrating the efficacy of positional clustering in detecting functional regulatory elements in mammals.