The location of the left-handedly curved DNA sequence affects exogenous DNA expression in vivo.
The intranuclear disposition of a plasmid is extremely important for transgene expression. The effects of a left-handedly curved sequence with high histone affinity on plasmid expression were examined in vivo. A naked luciferase-plasmid was delivered into mouse liver by a hydrodynamics-based injection, and the luciferase activities were quantitated at various time points. The location of the left-handedly curved sequence determined the transgene expression, without affecting the amount of intranuclear exogenous DNA. The plasmid containing the curved sequence at the location that results in the exposure of the TATA box out of the nucleosome core showed the highest expression. These results suggest that sequences with high histone affinity could control transgene expression from plasmids in vivo.
Kamiya
Hiroyuki
H
Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan. hirokam@pharm.hokudai.ac.jp
Fukunaga
Satoki
S
Ohyama
Takashi
T
Harashima
Hideyoshi
H
D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002522:Chlorocebus aethiops; D043542:DNA, Z-Form / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000737:chemistry*; D005786:Gene Expression Regulation / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009690:Nucleic Acid Conformation; D010957:Plasmids
D043542:DNA, Z-Form