Binding of elongation factor Spt6 to Iws1 provides an effective means for 
coupling eukaryotic mRNA synthesis, chromatin remodelling and mRNA export. We 
show that an N-terminal region of Spt6 (Spt6N) is responsible for interaction 
with Iws1. The crystallographic structures of Encephalitozoon cuniculi Iws1 and 
the Iws1/Spt6N complex reveal two conserved binding subdomains in Iws1. The 
first subdomain (one HEAT repeat; HEAT subdomain) is a putative 
phosphoprotein-binding site most likely involved in an Spt6-independent function 
of Iws1. The second subdomain (two ARM repeats; ARM subdomain) specifically 
recognizes a bipartite N-terminal region of Spt6. Mutations that alter this 
region of Spt6 cause severe phenotypes in vivo. Importantly, the ARM subdomain 
of Iws1 is conserved in several transcription factors, including TFIIS, Elongin 
A and Med26. We show that the homologous region in yeast TFIIS enables this 
factor to interact with SAGA and the Mediator subunits Spt8 and Med13, 
suggesting the molecular basis for TFIIS recruitment at promoters. Taken 
together, our results provide new structural information about the Iws1/Spt6 
complex and reveal a novel interaction domain used for the formation of 
transcription networks.