As Cobra1 is not known to bind DNA by itself, it may be recruited to its target genes by the three master regulators. Alternatively, Cobra1 could repress transcription through its putative interactions with other DNA-binding transcription repressors that play critical roles in ESC functions. Recent genome-wide analyses uncovered an unexpected CX-4945 transcriptional and chromatin status of the developmental genes that are repressed by the master regulators in ESCs. The majority of these genes experience transcription initiation, as evidenced by the presence of histone modification marks that are associated with active transcription initiation. Furthermore, Pol II can be detected at the promoter-proximal region of these transcriptionally inactive genes. The well-established biochemical function of NELF in polymerase pausing during transcription elongation would be consistent with a role of Cobra1 in keeping developmental genes in a poised transcriptional state. In this regard, it is somewhat surprising that Cobra1 knockdown significantly increases the total amount of promoter-associated polymerase at the Lef1 promoter-proximal region. Also proteins involved in translation show obvious quantitative expression changes. The amplitude of change remains low and variation in specific functional cascades is difficult to characterize, as already reported. One of the largest hindrances to identifying particular pathways affected by the drug is the high number of hypothetical proteins that show changes. These proteins can currently not be classified to a particular pathway, which will, however, improve over time. In addition, our data is in accordance with the observation of Gunasekera et al., who observed broad mRNA expression changes in parasites treated with CQ. These changes affected particularly ribosomal proteins, signaling molecules, protein processing , as well as RNA metabolism. There is a high degree of overlap between the functional group of proteins in the transcriptome data and our proteome study, however, the observed changes are less pronounced at the protein level. A direct and quantitative comparison of the proteome and transcriptome datasets has its limitations since parasite stages employed, synchronicity, drug doses and exposure times varied between the studies.We extended our studies to include other members of the MAP2K and MAPK gene families. Our strategy to allow partial open reading frames and improved secreted protein predictions in eukaryotic transcriptomes provides valuable tools for the analysis and annotation of eukaryotic genomes. We are currently evaluating the fluorescence emission spectrum of DAPI and related molecules when bound to various inositol pyrophosphates. Hence, it would be expected that malfunctions in factors necessary for secretion would affect the fertilizing potential of sperm. However, since secretion is a key cellular function necessary for many survival mechanisms, most mutations in these factors render animals unable to survive to reproductive age.