Eukaryotic promoters determine transcription start sites (TSSs), and are often enriched for transcription factor binding sites (TFBSs), which presumably play a major role in determining the location and activity of the TSS. In mammalian systems, proximal promoters are enriched for the CpG dinucleotide. The TFBSs that are enriched in proximal promoters (-200 bps to the TSS) are CCAAT, ETS, NRF1, SP1, E-Box, CRE, BoxA, and TATA. Only TATA occurs in a DNA strand dependent manner. In Drosophila, proximal promoters are AT rich and many putative TFBSs are enriched in proximal promoters. These sequences are different from those that occur in human promoters, except for TATA and E-Box, and many occur on a single strand of DNA giving directionality to the promoter. Thus, fundamental differences have arisen as promoters evolved in metazoans.