Spt5 Background Information RNA polymerase II (RNAP II) comprises a 12 subunit protein complex that mediates transcription (1). RNAP II contains a unique carboxy terminal domain (CTD), which consists of 52 repeats of the consensus heptapeptide Tyr-Ser-Pro-Thr-Ser-Pro-Ser (1). The RNAP II isoform with an unphosphorylated CTD associates with transcription initiation complexes, whereas the isoform with a phosphorylated CTD is involved in transcription elongation (1-3). The suppressor of Ty proteins Spt4 and Spt5, which are highly conserved from yeast to human, form a complex designated DSIF (for DRB-sensitivity-inducing factor) with the phosphorylated form of RNAP II (4,5). The DSIF complex mediates interactions between RNAP II and nucleosomes to positively regulate transcription elongation in conjunction with the Paf1- and FACT-RNAP II associated complexes (6,7). The activity of Spt4 and Spt5 depends upon the length of the CTD of RNAP II, the presence of certain phosphoreceptors within the CTD, and the function of at least three CTD kinases (7). The Spt5 protein, which localizes to the nucleus, contains a highly acidic amino terminus and a novel six amino acid repeat (S-T/A-W-G-G-A/Q) in the carboxy terminus (8).