We therefore examined 1 kilobase of genomic sequence immediately upstream of the ΔKal, Kal B and Kal C transcriptional start sites for the presence of consensus binding sites for these four transcription factors (Figure 10). Consensus sites for CREB, ΔFosB and MEF2A were not found in these regions. A consensus Sp1 site (GGGCGG) was identified close to the ΔKalrn transcriptional start site [53]; this site is perfectly conserved in mouse and rat. Consensus Sp1 sites, or close matches, were identified in the Kalrn B, Kalrn C and Kalrn A promoters, but are over 300 nucleotides from the transcriptional start site; none occur in the Kalrn D promoter (Figure 10). Because they are GC-rich, Sp1 sites are strongly affected by chromatin methylation [54]. Interfering pharmacologically with Sp1 function (e.g. with mithramycin) is known to block psychostimulant sensitization [51] and Sp1 binding to the proximal promoters of the mu opioid receptor has been clearly demonstrated [55].
