Position-effect variegation in Drosophila: the modifier Su(var)3-7 is a modular DNA-binding protein.

An increase in the dose of the Su(var)3-7 locus of Drosophila augments heterochromatin-promoted variegated silencing. The deduced protein sequence of Su(var)3-7 reveals seven widely spaced zinc fingers. We found that Su(var)3-7 has affinity for DNA in vitro and that the minimal protein sequence requirement for DNA binding is any module containing two zinc fingers and the interval between them. As Su(var)3-7 is a heterochromatin-associated protein, we tested its affinity for various satellite DNA sequences in vitro. The AATAT and 353-bp elements have the highest affinity. If affinity for satellite DNAs contributes to the presence of Su(var)3-7 in heterochromatin, a general affinity for DNA, or sequences yet to be determined, suggests a function in the genomic silencing of position-effect variegation: expansion of heterochromatin, whether continuous by spreading or discontinuous by pairing with sequence elements scattered through euchromatin, could use the affinity of Su(var)3-7 for DNA.