The formation of transcription-factor-binding sites is an important evolutionary process. Here, we show that methylation and deamination of CpG dinucleotides generate in vivo p53-binding sites in numerous Alu elements and in non-repetitive DNA in a species-specific manner. In light of this, we propose that the deamination of methylated CpGs constitutes a universal mechanism for de novo generation of various transcription-factor-binding sites in Alus.