Due to some insulators being upstream and others downstream of the promoters, the effect of insulators does not depend on their relative position to the promoters. Therefore, the reason for the directional effect of insulator functions remains unclear. Two gene loci have been found to influence insulator function by trans-activation. The nuclear protein encoded by gene S2J(Hw) recognizes insulators, and they only exert insulator effects after binding. Upon mutation of this gene, despite the insertion of an insulator into the y locus, the insulator effect is lost, leading to y expression in all tissues. Another gene locus is mod(mdg 4), whose mutation has the opposite effect of Su(Hw). That is, these mutations enhance the insulator function, eliminating the directional effect of insulator insulation and extending its effect, effectively blocking the enhancer effects on both upstream and downstream sides.