L. Kuras et D. Thomas, FUNCTIONAL-ANALYSIS OF MET4, A YEAST TRANSCRIPTIONAL ACTIVATOR RESPONSIVE TO S-ADENOSYLMETHIONINE, Molecular and cellular biology, 15(1), 1995, pp. 208-216
Transcription of the genes necessary for sulfur amino acid biosynthesi
s in Saccharomyces cerevisiae is dependent on Met4, a transcriptional
activator that belongs to the basic region-leucine zipper protein fami
ly. In this report, we show that one mechanism permitting the repressi
on of the sulfur network by S-adenosylmethionine (AdoMet) involves inh
ibition of the transcriptional activation function of Met4. Using a wi
de array of deleted LexA-Met4 fusion proteins as well as various Gal4-
Met4 hybrids, we identify the functional domains of Met4 and character
ize their relationship. Met4 appears to contain only one activation do
main, located in its N-terminal part. We demonstrate that this activat
ion domain functions in a constitutive manner and that AdoMet responsi
veness requires a distinct region of Met4. Furthermore, we show that w
hen fused to a heterologous activation domain, this inhibitory region
confers inhibition by AdoMet. Met4 contains another distinct functiona
l domain that appears to function as an antagonist of the inhibitory r
egion when intracellular AdoMet is low. On the basis of the presented
results, a model for intramolecular regulation of Met4 is proposed.