A complex regulatory circuit controls expression of many permeases and
enzymes involved in sulfur assimilation in the filamentous fungus Neu
rospora crassa. CYS3, the global positive-acting sulfur regulatory pro
tein, turns on the expression of structural genes that encode sulfur e
nzymes when N. crassa cells are limited for sulfur. Expression of the
cys-3 gene itself is highly regulated by negative-acting sulfur-contro
ller scon genes and by autogenous regulation. The CYS3 protein is loca
lized within the nucleus and contains a bZip DNA-binding motif and reg
ions rich in alanine and in proline that appear to function in trans a
ctivation. Amino acid substitutions for basic or neutral amino acids i
n the bZip domain of CYS3 lead to significant changes in its DNA-bindi
ng activity.