Fast-muscle-specific expression of human aldolase A transgenes.

activation of pM,we analyzed DNaseIhypersensitivity ina4.3-kbp fragment fromthe5'endofthehumanaldolase A gene. Fivehypersensitive sites were located near thetranscription initiation siteofeachpromoterinthose transgenic-mouse tissues inwhichthecorresponding promoter was active. Onlyone muscle-specific hypersensitive site was detected, mapping nearpM.Tofunctionally delimit theelements required formuscle-specific activity ofpM,we performed adeletion analysis ofthealdolase A5'region intransgenic mice. Ourresults show that a280-bp fragment containing 235bpofpM proximal upstream sequencestogether withthenoncoding M exon issufficient fortissue-specific expression ofpM.Whena putative MEF-2-binding site residing inthis proximal pM region ismutated, pM isstill active andno changeinitstissue specificity isdetected. Furthermore, we observed a modulation ofpM activity byelements lying further upstreamanddownstream frompM.Interestingly, pM was expressed ina tissue-specific way inalltransgenic miceinwhichthe280-bp region was present (32lines andsixfounder animals). Thisobservation ledustosuggest thattheproximal pM region contains elements that areabletooverride tosome extent theeffects ofthesurrounding chromatin.