Components of regulatory signaling pathways can control gene expression by phosphorylation of transcription factors, which in turn control expression of target genes. Members of the mitogen-activated protein kinase (MAPK) family physically associate with target genes. Pokholok et al. show that this phenomenon is much more common than previously expected. The authors performed a genome-wide screen for binding sites for members of the MAPK and cyclic adenosine monophosphate-dependent protein kinase (PKA) families. The MAPK proteins tested were physically associated with their target genes--in some cases at the promoter but in others along the transcribed region of the genes. The PKA family member Tpk1p was found to be associated with the transcribed portion of essentially all actively transcribed genes, whereas another family member, Tpk2p, was associated specifically with the transcribed region of genes encoding ribosomal subunits. Such analysis of target gene binding may reveal previously unrecognized targets of kinases and the signaling pathways in which they act.