Clearly, protein binding to DNA does not always necessitate regulatory function. To begin to address the functional Table 1 . Positional clustering based predictions of transcriptional regulatory sequences upstream of GABRs In total, we predict 15 orthologous pairs of regulatory sequences, representing 13 unique sequences. Comparing with known mammalian binding motifs, eight of the predictions show similarity to previously characterized TFBS, as indicated. Where no known binding motif exists, the corresponding in vitro EMSA and functional assay, if applicable, is indicated. Similar predictions are grouped together and aligned by hand. significance of our predicted regulatory motifs, we evaluated the effects of transfecting neurons with double-stranded oligonucleotides containing one of the GABRA4 novel binding motifs (dsA4O), as described above. GABRA4 is especially interesting given that it is regulated by brain derived neurotrophic factor (BDNF) after status epilepticus (31, 53) . Transfection with the dsA4O produced a significant downregulation of GABRA4 gene expression in neocortical neurons as monitored by quantitative real-time RT-PCR with no change after MOCK transfection or transfection with a dsO containing three copies of a cAMP regulatory element (CRE) (Figure 6 ).