This talk will summarize a biophysically motivated method (TRAP) for prediction of transcription factor binding sites and give some applications. Main applications are the identification of tissue specific transcription factors and the prediction of regulatory changes due to SNPs. Further, the talk will describe some indications that the division of promoters into two classes with high and low CpG contents, respectively, is of functional importance and helps in understanding mammalian promoters. In fact, the two classes of promoters display different features when it comes to binding site usage and tissue specific regulation. The dichotomy is further supported by an analysis of histone modifications in the promoters. There we observe that in a log-linear model relating histone modifications to expression level, different sets of modifications are respectively the most informative for prediction in the two classes of promoters. Taken together, we interpret this as indication that different regulatory mechanisms govern transcription in these two classes of promoters.