Combinatorial interactions of distinct enhancers are critical to recapitulate the endogenous expression of Lmo2. (a) The Lmo2 gene locus is drawn to scale. Exons are shown as black rectangles. Regulatory elements (-75/-70/-25/-12/pP/+1) are highlighted using shapes and distinct colours (-75 = orange diamond; -70 = green octagon; -25 = blue oval; dP = red rectangle; -12 = red triangle; +1 = purple triangle). (b) Transgenic animals were generated with many different combinations of the identified regulatory elements. The -75 enhancer and pP showed strong expression in endothelium, circulating erythrocytes and fetal liver. The -70 enhancer together with pP showed weak staining in endothelium and haematopoietic progenitor cells. The -25 or the -12 enhancer together with pP showed strong expression in endothelium and fetal liver. The +1 enhancer with pP gave rise to lacZ staining in the tail, apical ridge of the limbs, fetal liver and strong endothelium. Only when these elements were coupled together was a staining pattern corresponding to endogenous expression of Lmo2 seen . Strength of staining is indicated: +++, very strong; ++, intermediate; +, weak; -, not present.