MYOTUBE-SPECIFIC ACTIVITY OF THE HUMAN ALDOLASE A M-PROMOTER REQUIRESAN OVERLAPPING BINDING-SITE FOR NF1 AND MEF2 FACTORS IN ADDITION TO ABINDING-SITE (M1) FOR UNKNOWN PROTEINS

The human aldolase A gene is expressed in several tissues through the use of three alternative promoters. The activity of one of the promote rs, pM, is restricted to skeletal muscle. We reported previously that a proximal 280 bp pM fragment confers tissue-specific expression to a CAT reporter gene in transgenic mice. This small regulatory region dir ects expression to muscle composed mainly of fast-twitch fibers. Here we show that a minimal promoter fragment from base-pairs -164 to +45 i s sufficient to highly active pM during myoblast differentiation in ce ll culture and demonstrate that two DNA elements play a major role in this activation. These elements consist of a binding site (M1) for unk nown ubiquitous proteins and aa overlapping binding site for MEF2 and NF1 families of transcription factors. The NF1 factor constitute the m ain binding activity on the MEF2/NF1 site and, interestingly, some of the DNA-protein complexes that form with muscle nuclear extracts on th e NF1 element differ from those that form with non-muscular extracts. (C) 1995 Academic Press Limited