Reciprocal regulation of anaerobic and aerobic cell wall mannoprotein geneexpression in Saccharomyces cerevisiae

The DAN/TIR genes encode nine cell wall mannoproteins in Saccharomyces cere visiae which are expressed during anaerobiosis (DAN1, DAN2, DAN3, DAN4, TIR 1, TIR2, TIR3, TIR4, and TIP1). Most are expressed within an hour of an ana erobic shift, but DAN2 and DAN3 are expressed after about 3 h, At the same time, CWP1 and CWP2, the genes encoding the major mannoproteins, are down-r egulated, suggesting that there is a programmed remodeling of the cell wall in which Cwp1 and Cwp2 are replaced by nine anaerobic counterparts. TIP1, TIR1, TIR2, and TIR4 are also induced during cold shock. Correspondingly, C WP1 is down-regulated during cold shock. As reported elsewhere, Mox4 is a h eme-inhibited activator, and Mot3 is a heme-induced repressor of the DAN/TI R genes (but not of TIP1). We show that CWP2 (but not CWP1) is controlled b y the same factors, but in reverse fashion-primarily by Mot3 (which can fun ction as either an activator or repressor) but also by Mox4, accounting for the reciprocal regulation of the two groups of genes. Disruptions of TIR1, TIR3, or TIR4 prevent anaerobic growth, indicating that each protein is es sential for anaerobic adaptation. The Dan/Tir and Cwp proteins are homologo us, with the greatest similarities shown within three subgroups: the Dan pr oteins, the Tip and Tir proteins, and, more distantly, the Cwp proteins. Th e clustering of homology corresponds to differences in expression: the Tip and Tir proteins are expressed during hypoxia and cold shock, the Dan prote ins are more stringently repressed by oxygen and insensitive to cold shock, and the Cnp proteins are oppositely regulated by oxygen and temperature.