The function of insulators is directional, a discovery made in fruit fly experiments. Insertion of the transposable element gypsy into the yellow gene locus on Drosophila melanogaster results in the inactivation of the y gene in some tissues, while it remains active in others, due to a insulator sequence at one end of gypsy. Different effects on gene activity are observed when gypsy is inserted at different positions on the y gene locus. This is because the activity of the y gene is regulated by four enhancers; when the insulator is inserted upstream of the promoter, it blocks gene activation in wing blade and body cuticle tissues (from upstream enhancers), but does not block the expression of the y gene in bristle and tarsal claw tissues (from downstream enhancers). Since some enhancers are upstream and others downstream of the promoter, the effect of the insulator does not depend on the relative position to the promoter. Therefore, the reason for the directional effect of insulators has not been fully understood. Two gene loci have been found to affect the function of insulators in a trans-activating manner. The nuclear protein encoded by gene S2J (Hw) recognizes insulators, and insulator binding is necessary for insulation. When this gene mutates, even with the insulator inserted into the y gene locus, the insulation effect is lost, and the y gene is expressed in all tissues. Another gene locus is mod (mdg 4); its mutation has the opposite effect of Su(Hw), meaning that these mutations enhance insulation, causing the insulation effect to lose its directionality and extend, blocking the effects of enhancers on both upstream and downstream sides.