MAZ-DEPENDENT TERMINATION BETWEEN CLOSELY SPACED HUMAN-COMPLEMENT GENES

The zinc finger protein MAZ, originally identified as a factor that bi nds to the c-myc P2 promoter, is associated with transcriptional termi nation, As shown in these studies, a termination sequence between the closely spaced human complement genes C2 and Factor B contains a prote in binding site which interacts with three different proteins in vitro , Binding of one of these factors, MAZ, correlates with activity of th e C2 termination sequence in vivo, Cloned MAZ was used to obtain a con sensus binding site, G(5)AG(5). This allowed identification of new sit es, between the closely spaced human genes g11 and C4 and within an in tron of the mouse IgM-D gene, where termination is known to occur and regulate the expression of IgD, The g11 and IgM MAZ sites lie within s equences that have activity in a termination assay and, furthermore, m utation of C2 or g11 MAZ sites severely reduces termination activity, MAZ bends DNA, and inherently bent DNA is highly active as a terminato r, suggesting that MAZ-induced bending is important for C2 and g11 ter mination, We propose that MAZ sites exist in promoters which require p rotection against transcriptional interference, such as those of close ly spaced genes, to cause efficient termination, The MAZ consensus seq uence will facilitate the identification of further sites.