The comprehensive mapping of transcription regulatory regions in the genome of higher eukaryotes and the analysis of transcription factors recruited to these sites are major challenges. The multitude of general (co)factors, chromatin modifying and remodeling complexes involved in transcription is staggering and estimated to involve up to 6% of the protein coding genes in mammalian genomes.

To gain insight into the organization and factor composition of promoters and to identify novel promoters, we performed ChIP-on-chip using a monoclonal antibody against the TBP. A remarkably large proportion of novel TBP binding sites located in introns or in annotation waste lands are indeed sites of transcription initiation suggesting that a much larger fraction of the human genome may be transcribed. ChIP-on-chip analysis for >30 transcription factors on >1000 known and novel TBP binding sites revealed distinct profiles for general transcription factors.

Genome wide profiling with the transcription factors ER, p53 and TCF4 revealed that they regulate their target genes mostly from a distance rather than through proximal promoters. Interestingly, TCF4 binding sites frequently cluster in the vicinity of putative target genes. Motif searches revealed that a rather large number of the in vivo target sites did not contain the expected cis-acting sequence indicating that transcription regulation frequently involves cross-talk with other factors.

Our mass spectrometric studies on histone modifications of the malaria parasite Plasmodium falciparum showed a predominance of euchromatic marks such as H3 acetylation and methylation (H3K4me) and virtual lack of repressive marks (H3K9me and H3K27me). In contrast to genome wide studies from yeast to human, H3K4me3 and H3K9ac are nearly uniformly spread over active as well as inactive genes. Our study strongly suggests that P. falciparum has diverted its well conserved epigenetic machinery into a specialized function.