The eukaryotic transcription elongation factor DSIF [DRB 
(5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole) sensitivity-inducing factor] 
is composed of two subunits, hSpt4 and hSpt5, which are homologous to the yeast 
factors Spt4 and Spt5. DSIF is involved in regulating the processivity of RNA 
polymerase II and plays an essential role in transcriptional activation of 
eukaryotes. At several eukaryotic promoters, DSIF, together with NELF (negative 
elongation factor), leads to promoter-proximal pausing of RNA polymerase II. In 
the present paper we describe the crystal structure of hSpt4 in complex with the 
dimerization region of hSpt5 (amino acids 176-273) at a resolution of 1.55 A (1 
A=0.1 nm). The heterodimer shows high structural similarity to its homologue 
from Saccharomyces cerevisiae. Furthermore, hSpt5-NGN is structurally similar to 
the NTD (N-terminal domain) of the bacterial transcription factor NusG. A 
homologue for hSpt4 has not yet been found in bacteria. However, the archaeal 
transcription factor RpoE" appears to be distantly related. Although a 
comparison of the NusG-NTD of Escherichia coli with hSpt5 revealed a similarity 
of the three-dimensional structures, interaction of E. coli NusG-NTD with hSpt4 
could not be observed by NMR titration experiments. A conserved glutamate 
residue, which was shown to be crucial for dimerization in yeast, is also 
involved in the human heterodimer, but is substituted for a glutamine residue in 
Escherichia coli NusG. However, exchanging the glutamine for glutamate proved 
not to be sufficient to induce hSpt4 binding.