Regulatory mechanisms controlling expression of the DAN/TIR mannoprotein genes during anaerobic remodeling of the cell wall in Saccharomyces cerevisiae
Ne. Abramova et al., Regulatory mechanisms controlling expression of the DAN/TIR mannoprotein genes during anaerobic remodeling of the cell wall in Saccharomyces cerevisiae, GENETICS, 157(3), 2001, pp. 1169-1177
The DAN/TIR genes of Saccharomyces cerevisiae encode homologous mannoprotei
ns, some of which are essential for anaerobic growth. Expression of these g
enes is induced during anaerobiosis and in some cases during cold shock. We
show that several heme-responsive mechanisms combine to regulate DAN/TIR g
ene expression. The first mechanism employs two repression factors, Mox1 an
d Mox2, and an activation factor, Mox4 (for mannoprotein regulation by oxyg
en). The genes encoding these proteins were identified by selecting for rec
essive mutants with altered regulation of a dan1::ura3fusion. MOX4 is ident
ical to UPC2, encoding a binucleate zinc cluster protein controlling expres
sion of an anaerobic sterol transport system. Mox4/Upc2 is required for exp
ression of all the DAN/TIR genes. It appears to act through a consensus seq
uence termed the AR1 site, as does Mox2. The noninducible mox4 Delta allele
was epistatic to the constitutive mox1 and mox2 mutations, suggesting that
Mox1 and Mox2 modulate activation by Mox4 in a heme-dependent fashion. Mut
ations in a putative repression domain in Mox4 caused constitutive expressi
on of the DAN/TIR genes, indicating a role for this domain in heme repressi
on. MOX4 expression is induced both in anaerobic and cold-shocked cells, so
heme may also regulate DAN/TIR expression through inhibition of expression
of MOX4. Indeed, ectopic expression of MOX4 in aerobic cells resulted in p
artially constitutive expression of DAN1. Heme also regulates expression of
some of the DAN/TIR genes through the Rox7 repressor, which also controls
expression of the hypoxic gene ANB1. In addition Rox1, another heme-respons
ive repressor, and the global repressors Tup1 and Ssn6 are also required fo
r full aerobic repression of these genes.