We found Nhp6a/b yeast HMG-box chromatin-associated architectural factors and 
Ssn6 (Cyc8) corepressor to be crucial transcriptional coactivators of FRE2 gene. 
FRE2 encoding a plasma membrane ferric reductase is induced by the 
iron-responsive, DNA-binding, transcriptional activator Aft1. We have shown that 
Nhp6 interacts directly with the Aft1 N-half, including the DNA-binding region, 
to facilitate Aft1 binding at FRE2 UAS. Ssn6 also interacts directly with the 
Aft1 N-half and is recruited on FRE2 promoter only in the presence of both Aft1 
and Nhp6. This Nhp6/Ssn6 role in Aft1-mediated transcription is FRE2 promoter 
context specific, and both regulators are required for activation-dependent 
chromatin remodeling. Our results provide the first in vivo biochemical evidence 
for nonsequence-specific HMG-box protein-facilitated recruitment of a yeast 
gene-specific transactivator to its DNA target site and for Nhp6-mediated Ssn6 
promoter recruitment. Ssn6 has an explicitly coactivating role on FRE2 promoter 
only upon induction. Therefore, transcriptional activation in response to iron 
availability involves multiple protein interactions between the Aft1 
iron-responsive DNA-binding factor and global regulators such as Nhp6 and Ssn6.